ACS Publications. Most Trusted. Most Cited. Most Read
Quick View

OR SEARCH CITATIONS

My Activity
Publications
CONTENT TYPES

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:ACS Cent. Sci. 2021, 7, 7, 1166-1175
RETURN TO ISSUEPREVResearch ArticleNEXT

Janus Emulsion Biosensors for Anti-SARS-CoV-2 Spike Antibody

Cite this: ACS Cent. Sci. 2021, 7, 7, 1166–1175
Publication Date (Web):June 16, 2021
https://doi.org/10.1021/acscentsci.1c00173

Copyright © 2022 The Authors. Published by American Chemical Society. This publication is licensed under

CC-BY-NC-ND 4.0.
  • Open Access

Article Views

3758

Altmetric

-

Citations

19
LEARN ABOUT THESE METRICS
PDF (11 MB)
Get e-Alerts
Supporting Info (1)»
SUBJECTS:

Abstract

High Resolution Image
Download MS PowerPoint Slide

The spread of the COVID-19 pandemic around the world has revealed that it is urgently important to develop rapid and inexpensive assays for antibodies in general and anti-SARS-CoV-2 IgG antibody (anti-SARS-CoV-2 spike glycoprotein S1 antibody) in particular. Herein we report a method to detect the anti-SARS-CoV-2 spike antibody level by using Janus emulsions or Janus particles as biosensors. Janus emulsions are composed of two immiscible hydrocarbon and fluorocarbon oils. The hydrocarbon/water interfaces are functionalized with a secondary antibody of IgG protein and SARS-CoV-2 spike receptor binding domain (RBD), to produce two different Janus emulsions. Mixtures of these Janus droplets enable the detection of the anti-SARS-CoV-2 spike IgG antibody in an agglutination assay caused by the antibody’s binding to both the secondary antibody of IgG antibody and SARS-CoV-2 spike protein RBD. Both qualitative optical images and quantitative fluorescence spectra are able to detect the level of anti-SARS-CoV-2 spike antibody at concentrations as low as 0.2 μg/mL in 2 h. The detection results of clinical human serum samples using this agglutination assay confirm that this method is applicable to clinical samples with good sensitivity and specificity. The reported method is generalizable and can be used to detect other analytes by attaching different biomolecular recognition elements to the surface of the Janus droplets.

This publication is licensed under

CC-BY-NC-ND 4.0.
  • cc licence
  • by licence
  • nc licence
  • nd licence

Synopsis

An efficient, sensitive and less expensive method of using Janus emulsions or Janus particles for the detection of the anti-SARS-CoV-2 spike IgG antibody in human serum is described.

Introduction

ARTICLE SECTIONS
Jump To
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), is the novel coronavirus responsible for the global COVID-19 pandemic that began in 2019. (1,2) Coronavirus disease has some common manifestations such as cough, fever, fatigue, and diarrhea. However, many patients are not receptive to treatments (3−6) and develop breathing difficulties, multiple organ failure, cytokine storm syndromes and blood clots that can lead to long-term organ damage and mortality. (7−11) Effective vaccination, which could prevent continuous or repeated pandemic has begun; (12−14) however, there will be a continuing need for methods to evaluate immunity. As a result, rapid methods to detect the anti-SARS-CoV-2 antibody will be a key component of combating the pandemic. The spike protein of the novel coronavirus is a glycosylated protein that assembled on the surface of the virus SARS-CoV-2, (15,16) and is essential for receptor recognition of the host cell’s membrane. (17−21) The presence of anti-SARS-CoV-2 spike IgG antibody in human blood is a primary biomarker to evaluate immunity and diagnose SARS-CoV-2 infection. (22) As a result, rapid, inexpensive, and uncomplicated methods are needed to test for the anti-SARS-CoV-2 spike IgG antibody.
Water dispersed droplets can be produced by a number of emulsification methods, (23) and are important components of cosmetic, (24,25) medicine, (26−28) and food. (29−31) Janus droplets or double emulsions have found applications in the development of pharmaceuticals, (32,33) biosensing, (34−38) and in dynamic optics. (39,40) For example, complex emulsions behave as microlens systems that can be used to measure enzyme activity through catalytic processes modification of surfactants that cause changes in droplet morphology and hence the optical transmission. (39) Changes in morphology can also produce sensing responses when measuring emissive signals from the interior of the droplets. In this case, the direction of the emission is highly sensitive to the morphology and can be used to detect the existence of carbohydrates or bacteria. (36)
We report herein, the application of bioconjugated Janus emulsions composed of equal amounts of fluorocarbon and hydrocarbon oils to detect the anti-SARS-CoV-2 spike IgG antibody. Functionalizing the hydrocarbon and continuous phase (water) interfaces of Janus droplets separately with SARS-CoV-2 spike RBD and Goat Anti-Human IgG antibody produces two complementary emulsions. Mixtures of these two droplet-bioconjugates in a 1:1 ratio are used to detect the anti-SARS-CoV-2 spike antibody. The Goat Anti-Human IgG antibody is a secondary antibody of IgG antibody and binds to the Fc domain of anti-SARS-CoV-2 spike IgG antibody. The SARS-CoV-2 spike RBD is the antigen and hence binds to the Fab domain of the anti-SARS-CoV-2 spike antibody. (41) When not constrained, Janus emulsions orient with their densest phase on the bottom as a result of gravity. However, agglutination triggered by binding of the anti-SARS-CoV-2 spike antibody to the complementary droplets interrupts this ideal alignment. To quantify the degree of agglutination, we have labeled Janus emulsions with two different dyes. Specifically, we have designed dye pairs, one emissive and one nonemissive, that segregate into the two phases of each droplet. The nonemissive dye serves as a blocking element that absorbs both the excitation light and emitted light from the emissive dye. In a configuration wherein the path of the excitation and emitted light must both go through the blocker dye phase, a very low amount of fluorescence is observed because few photons reach the emissive dye, and any emission is further absorbed by the blocker dye prior to impinging on the detector. To achieve this blocking effect, excitation and detected wavelengths are matched to the Janus droplets such that there is minimal emission when they are in their density aligned state. However, when droplets are agglutinated around an anti-SARS-CoV-2 spike antibody the alignment is changed such that the blocker dye is not fully in the path of the excitation and emission light. As a result, the level of anti-SARS-CoV-2 spike antibody can be determined by the intensity of a fluorescence signal. We also demonstrate that this process can be applied to solidified (polymerized) Janus emulsions. The polymerized Janus particles offer an increase in stability that can extend the utility of this method to demanding applications that may cause breakdown of a pure liquid emulsion. Moreover, we perform the agglutination assay with clinical human sera from COVID-19 patients, and the results suggest that this method is applicable to the detection of anti-SARS-CoV-2 spike IgG antibody in clinical samples.

Results and Discussion

ARTICLE SECTIONS
Jump To

Bioconjugation and the Agglutination Assay

Figure 1a illustrates the chemical structure of the block copolymer surfactant P-TCO, which contains an acrylic acid block partially amidated with transcyclooctene (TCO) block, for bioconjugation in a click reaction with tetrazine. (34,42−44) P-TCO (1 mg/mL) in dietheylbenzene (DEB) is mixed in a 1:1 ratio with fluorocarbon solvent (3-ethoxyperfluoro(2-methylhexane), HFE7500). The mixture is heated above the upper consolute temperature (40 °C) and dispersed into an aqueous continuous phase containing PBS buffer and surfactants (0.5 wt % Zonyl/0.5 wt % Tween 20, 1:1 (v/v)). Cooling of the emulsion results in phase separation to the Janus state and, as illustrated in Figure 1b, interfacial bioconjugation is performed in situ. In this process we add 60 μL of Tetrazine-Goat Anti-Human IgG antibody (1.0 mg/mL) into the continuous phase and allow it to react at room temperature overnight on a rocker. Similarly, 60 μL of Tetrazine-SARS-CoV-2 spike protein RBD (0.1 mg/mL) added to the continuous phase results in bioconjugation after overnight on a rocker at room temperature. After the quantification (Figure S1, see Supporting Information for details), we calculated the area per Goat Anti-Human IgG antibody and the area per SARS-CoV-2 spike protein RBD on the surface of Janus droplets, which are 4300 nm2/antibody and 6500 nm2/protein, respectively. Droplets are washed three times with 0.5 mL of 0.5 wt % Zonyl/0.5 wt % Tween 20 1:1 (v/v) solution to remove the unreacted reagents. As shown in Figure 1c, the optical image of the 1:1 mixture of the droplets with Goat Anti-Human IgG antibody or SARS-CoV-2 spike protein RBD reveals that all the droplets are gravity oriented when no anti-SARS-CoV-2 spike antibody is present in the continuous phase. This latter observation confirms there is no aggregation or nonspecific interactions between bioconjugated droplets. Control experiments are conducted to reveal there is no agglutination without the analyte anti-SARS-CoV-2 spike antibody and the Janus emulsions further do not agglutinate in serum solutions that also lack the antibody (Figure S2–S4).

Figure 1

Figure 1. General scheme for interfacial bioconjugation of the Janus droplets’ hydrocarbon phase. (a) Chemical structure of polymer P-TCO. (b) Bioconjugation scheme of Tetrazine Goat Anti-Human IgG antibody and Tetrazine-SARS-CoV-2 spike protein receptor binding domain (RBD) to P-TCO at the hydrocarbon–water interface of Janus droplets. (c) Optical image of 1:1 mixture of P-TCO polydisperse Janus droplets after bioconjugation with SARS-CoV-2 spike RBD and P-TCO Janus droplets after bioconjugation with Goat Anti-Human IgG antibody. Scale bar = 50 μm.

High Resolution Image
Download MS PowerPoint Slide
Two droplet variants bioconjugated with Goat Anti-Human IgG antibody and SARS-CoV-2 spike protein RBD are used in a 1:1 ratio in assays for the anti-SARS-CoV-2 spike antibody. The agglutination detection mechanism results in tipping of droplets from their equilibrium density (gravity) alignment. To allow for the anti-SARS-CoV-2 spike IgG antibody to optimally agglutinate, we have designed the system to have multiple interactions between the droplets and this target biomolecule. The Goat-Anti-Human IgG antibody, as a secondary antibody to IgG binds to the Fc domain, and does not prevent the SARS-CoV-2 spike protein RBD from binding to the Fab domains. To test this mechanism, we added anti-SARS-CoV-2 spike IgG antibody to the continuous phase of a mixture of the bioconjugated droplets for 2 h at room temperature on a rocker (Figure 2a). The microscope images in Figure 2b,c reveal the agglutinations formed by the monodispersed droplets after being treated with 60 μg/mL or 1 μg/mL of anti-SARS-CoV-2 spike antibody, respectively. We clearly observe the formation of agglutinations in the images and as expected there are more agglutinations at high concentrations of anti-SARS-CoV-2 spike antibody (Figure 2b) than at low concentrations (Figure 2c). We also added 60 μg/mL of anti-SARS-CoV-2 spike IgG antibody into the continuous phase of Janus droplets conjugated with SARS-CoV-2 spike protein RBD. We observed formation of agglutinations as shown in Figure S5, but the amount of agglutination is much less than adding the antibody to the 1:1 mixture since only the two arms of antibody are available for binding in this case.

Figure 2

Figure 2. Agglutination assay achieved by adding anti-SARS-CoV-2 spike IgG antibody into the continuous phase of the mixture of Janus droplets. (a) Agglutination scheme with the addition of anti-SARS-CoV-2 spike antibody. (b) Bright field microscope image of a 1:1 mixture of Goat Anti-Human IgG antibody and SARS-CoV-2 spike protein RBD bioconjugated monodispersed droplets, 2 h after the addition of 60 μg/mL anti-SARS-CoV-2 spike antibody. The scatter light of the agglutinated droplets appears as dark objects. (c) The same assay as in panel b, but with 1 μg/mL anti-SARS-CoV-2 spike antibody. Scale bar = 50 μm.

High Resolution Image
Download MS PowerPoint Slide

Quantification of Agglutinations by Fluorescence Spectra

It is possible to quantify agglutination events using optical imaging and image processing software. (37) However, a simplified method is to quantitatively measure the degree of agglutination using fluorescence signals under the conditions of directional excitation and emission detection. The emissive and blocker dyes have orthogonal solubility in the Janus droplets and are strictly partitioned between the fluorocarbon and hydrocarbon phases. As shown in Figure 3a, a nonemissive blocker dye sub-PC localizes in the hydrocarbon phase and a red emissive fluorescent dye F-PBI is only present in the fluorocarbon phase. (45)Figure 3b schematically represents the formation of agglutinations of 1:1 mixtures of Janus droplets bioconjugated with Goat anti-Human IgG antibody or SARS-CoV-2 spike RBD protein after the addition of anti-SARS-CoV-2 spike antibody. Figure 3c shows the optical image of droplets before the addition of anti-SARS-CoV-2 spike antibody indicating equilibrium droplet density alignment in the absence of agglutination. Adding 20 μg/mL of anti-SARS-CoV-2 spike IgG antibody to the continuous phase of the mixture of the bioconjugated droplets for 2 h reveals agglutination (Figure 3d).

Figure 3

Figure 3. Illustration of the agglutination assay with Janus droplets containing blocker dye sub-PC in the hydrocarbon phase and emissive dye F-PBI in the fluorocarbon phase. (a) Scheme of a P-TCO functionalized Janus droplet with a blocker sub-PC dye in the hydrocarbon phase and the F-PBI red emissive dye in the fluorocarbon phase. (b) Agglutination scheme with the two-dye system. (c) Optical microscope image of the fully bioconjugated monodispersed droplets (1:1 mixture) that also contain the two dyes showing their aligned state without the addition of anti-SARS-CoV-2 spike antibody. (d) Optical microscope image of the same 1:1 mixture as in part c, but with the addition of anti-SARS-CoV-2 spike antibody at a concentration of 20 μg/mL after 2 h. Scale bar = 50 μm.

High Resolution Image
Download MS PowerPoint Slide
Agglutination assays with the Janus droplets containing F-PBI and sub-PC dyes provide a fluorescence emission intensity that correlates with the concentration of anti-SARS-CoV-2 spike antibody when measurements are performed as schematically shown in Figure 4a. A bifurcated fiber-optic probe is positioned over the droplets, allowing for directional excitation and emission. Droplets have an equilibrium vertical alignment as a result of the higher density of the fluorocarbon phase, and in this configuration the blocker dye sub-PC is on the top and in the optical path. The result is that the emissive dye F-PBI dissolved in the fluorocarbon phase is not excited efficiently because the blocker dye absorbs the 361 nm light. Additionally, if any stray light reaches F-PBI, the blocker dye absorbs the red emission (λmax = 580 nm) because it is in the light path to the fiber optic. However, with the addition of anti-SARS-CoV-2 spike antibody and the formation of agglutinations, some droplets are tilted, and the fluorocarbon phase will be exposed to the excitation light, thereby creating an emission that is easily detected. Figure 4b details the fluorescence spectra of an assay using droplets containing dyes that were incubated with anti-SARS-CoV-2 spike antibody at different concentrations. Figure 4c shows the correlation of the relative fluorescence intensity at 580 nm and the concentration of anti-SARS-CoV-2 spike antibody. The relative fluorescence intensity at 580 nm in Figure 4c is calculated by the fluorescence spectra shown in Figure 4b. The relative fluorescence intensity at 580 nm is the fluorescence intensity of the spectrum of the control group (treated with 0 μg/mL of anti-SARS-CoV-2 spike antibody) at 580 nm to be divided by the fluorescence intensity of other spectra at 580 nm. The data are fit to a sigmoidal modal to provide the general trend. The results are consistent with the optical images, and with increasing agglutination, the emission intensity grows. As revealed in Figure 4b,c, the limit of detection of anti-SARS-CoV-2 spike antibody is 0.2 μg/mL.

Figure 4

Figure 4. Quantification of agglutination assay by measuring the fluorescence spectra. (a) Schematic of excitation and detection of fluorescence from the naturally oriented or agglutinated dye containing emulsions. Light is only able to reach the red dye when the droplets are tilted in the agglutinated structure. (b) Fluorescence spectra (λex = 361 nm) of 1:1 mixture of dye containing fully bioconjugated Janus droplets with the addition of anti-SARS-CoV-2 spike antibody at different concentrations. Note that the fluorescence intensity increases with concentration. (c) Correlation of concentration of anti-SARS-CoV-2 spike antibody and relative fluorescence intensity at 580 nm. All error bars are standard deviation calculated from three independent experiments (n = 3), and the asterisks (∗∗) represent statistical significance (**p ≤ 0.01).

High Resolution Image
Download MS PowerPoint Slide

Bottom Reading Scheme for Agglutination Quantification

Many samples, such as whole blood, are highly scattering and can complicate the assay shown in Figure 4. As a result, we have developed a bottom reading scheme as shown in Figure 5. This scheme makes use of the same bioconjugation method but requires the inversion of the blocker dye and emissive dye positions. We chose commercial Lumogen F Orange 240 as the hydrocarbon soluble emissive dye. To create a suitable blocker dye, we synthesized a fluorous soluble, nonemissive blocker dye based on the black hole quencher (BHQ) family of dyes (Figure 5a). This material, F-BHQ, dissolves in HFE7500 and absorbs the 535 nm emission from Lumogen F Orange 240 (synthesis procedures and characterizations are shown in Figures S6–S14). Figure 5b shows the optical image of the two dyes in their respective phases under visible light or UV light. Simple visual inspection confirms the orthogonal solubility, and it should be noted that the F-BHQ in the bottom fluorocarbon phase is completely dark under visible light or UV light. A plot of the ratio of molar extinction coefficients of Lumogen F Orange 240 and F-BHQ reveals that 400 nm is the most efficient wavelength for blocking the excitation light (Figure S15). Figure 5c shows the bottom reading two-dye assay configuration. As mentioned before, in the droplets equilibrium configuration the denser fluorocarbon will normally be located at the bottom. As a result, in the nonagglutinated state the blocker dye F-BHQ will be at the bottom and the emissive dye Lumogen F Orange 240 will be on the top. Locating the detector and light source (the bifurcated fiber-optic) at the bottom of a glass analysis dish, reveals minimal emission with 400 nm excitation in the absence of anti-SARS-CoV-2 spike antibody. Agglutination with the addition of anti-SARS-CoV-2 spike antibody causes droplet tilting, and the hydrocarbon phase containing emissive dye is exposed to the light source and increased emissive signals are detected. Figure 5d shows the fluorescence spectra of the 1:1 mixture of the bioconjugated Janus droplets with this dye pair after being treated with different concentrations of anti-SARS-CoV-2 spike IgG antibody. With higher concentration of anti-SARS-CoV-2 spike antibody, the emissive signal at 535 nm increases. The correlation of concentration of anti-SARS-CoV-2 spike antibody and relative fluorescence intensity at 535 nm indicates a limit of detection of 0.2 μg/mL (Figure 5e).

Figure 5

Figure 5. Illustrations of Janus droplets containing emissive Lumogen F Orange 240 dye in the hydrocarbon phase and blocker dye F-BHQ in the fluorocarbon phase and agglutination quantification. (a) A Janus droplet having an emissive perylene dye (Lumogen F Orange 240) in the hydrocarbon phase and a nonemissive dye (F-BHQ) in the fluorocarbon phase. (b) Optical image of Lumogen F Orange 240 in DEB and F-BHQ in HFE7500 under normal or UV light. (c) Bottom excitation and detection scheme of Janus droplets containing F-BHQ and Lumogen F Orange 240. (d) Fluorescence spectra (λex = 400 nm) of a 1:1 mixture of bioconjugated Janus droplets containing of F-BHQ dye in the fluorocarbon phase, P-TCO, and Lumogen F Orange 240 dye in the hydrocarbon phase, after the addition of anti-SARS-CoV-2 spike antibody at different concentrations. (e) Correlation of concentration of anti-SARS-CoV-2 spike antibody and relative fluorescence intensity at 535 nm. All error bars are standard deviations calculated from three independent experiments (n = 3), and the asterisks (∗∗) represent statistical significance (**p ≤ 0.01).

High Resolution Image
Download MS PowerPoint Slide

Agglutination Assay with Polymerized Janus Droplets

To create assays with additional robustness, we have created a polymerized version of our top-read assay. Figure 6a schematically illustrates the preparation, bioconjugation and polymerization of the Janus droplets. Polymerizable Janus droplets are created by replacing hydrocarbon/fluorocarbon oils in emulsion droplets with photopolymerizable liquid formulations that consist of hydrocarbon and fluorocarbon oligomers and cross-linkers. Specifically, fluorinated acrylate oligomer, fluorinated cross-linker, 1,4-butanediol diacrylate, and trimethylolpropane ethoxylate triacrylate are used as the dispersed phase, and 1 wt % of phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (BAPO) is used as the photo initiator. P-TCO is dissolved in the hydrocarbon phase as before, and its role as a surfactant allows for prepolymerization bioconjugation with Goat anti-Human IgG antibody or SARS-CoV-2 Spike protein RBD. To achieve comparable agglutination results, twice the protein concentration is required in the bioconjugation of the Janus droplets. After bioconjugation, the Janus droplets are cooled in ice and polymerization is photoinitiated by irradiating with 365 nm UV light (4.1 W) for 30 min. The cooling is required to ensure phase separation as maintained throughout the polymerization. The photopolymerized solid Janus particles are then evaluated in agglutination assays. Similar to the other assays, we added anti-SARS-CoV-2 spike antibody into the continuous phase of the 1:1 mixture of two bioconjugated and dyed Janus particles for 2 h. Figure 6b shows the optical image of the Janus particles before the addition of anti-SARS-CoV-2 spike antibody indicating that they are naturally aligned without anti-SARS-CoV-2 spike antibody. Figure 6c shows the formation of agglutinations after adding anti-SARS-CoV-2 spike antibody to the 1:1 mixture of polymerized Janus droplets (Janus particles). A SEM image of the Janus particles is presented in Figure 6d indicating the success of polymerization, and the particles are still round and Janus in nature. The photo-cross-linking process is also studied by ATR FTIR (Figure S16). Before UV irradiation, the IR spectrum of the photopolymerizable formulation presented the C═C stretching vibration band (at around 1625 cm–1) and the ═CH2 in-plane deformation band (at around 1410 cm–1) of the acrylate units. After 30 min of UV light irradiation, complete polymerization of the emulsions was confirmed by the disappearance of the acrylate bands in the FTIR spectrum. Fluorescence spectra are measured to quantify the formation of agglutinations upon the exposure to different concentrations of anti-SARS-CoV-2 spike antibody as shown in Figure 6e,f. Similar to the Janus droplets systems, the fluorescence intensity increases with the increase of the concentration of anti-SARS-CoV-2 spike antibody, and we can detect anti-SARS-CoV-2 spike antibody at or above the concentrations of 0.2 μg/mL using the polymerized Janus particles.

Figure 6

Figure 6. Polymerization of Janus droplets to form Janus particles. (a) Schematic illustration of the polymerization of Janus droplets and their agglutination. (b) Optical image of Janus particles before the addition of anti-SARS-CoV-2 spike antibody. Scale bar = 50 μm. (c) Optical image of 1:1 mixture of Janus particles 2 h after the addition of 20 μg/mL of anti-SARS-CoV-2 spike antibody. The red circles on the image signify the agglutinations of Janus particles. Note that some minor agglutinations are not circled to minimize clutter in the image. Scale bar = 50 μm. (d) SEM image of Janus particles after polymerization. (e) Fluorescence spectra (λex = 361 nm) of particles containing of F-PBI dye in the fluorocarbon phase, P-TCO, and sub-PC dye in the hydrocarbon phase, after addition of anti-SARS-CoV-2 spike antibody at different concentrations. (f) Correlation of concentration of anti-SARS-CoV-2 spike antibody and relative fluorescence intensity at 588 nm. All error bars are standard deviation calculated from three independent experiments (n = 3), the asterisks (∗∗) represent statistical significance (**p ≤ 0.01).

High Resolution Image
Download MS PowerPoint Slide

Agglutination Assay for Detection of Anti-SARS-CoV-2 Spike IgG Antibody in Clinical Human Sera

After verifying that the agglutination scheme could detect the anti-SARS-CoV-2 spike IgG antibody with a low limit of detection, we use the top-read agglutination assay for the sensing of the anti-SARS-CoV-2 spike IgG antibody in clinical human sera from COVID-19 patients. We choose a top-read scheme since it is more basic, and if a top-read scheme could achieve good sensitivity, the other two methods might achieve even better results. Figure 7a and Figure S17 summarize the calculated concentrations of anti-SARS-CoV-2 spike IgG antibody in human sera and the fluorescence spectra. The calculated antibody concentrations of the clinical samples are relative to the model antibody. We measured the anti-SARS-CoV-2 spike antibody concentration of 10 serum samples from COVID-19 patients which are known to have anti-SARS-CoV-2 spike IgG antibody, five serum samples from normal patients who are negative for SARS-CoV-2, three serum samples from normal patients who are negative for SARS-CoV-2 but have anti-Influenza IgG antibody, and three serum samples from patients who are negative for SARS-CoV-2 but have anti-MERS-CoV spike antibody. The known details about the positive clinical samples are shown in Table S1. Sera are added to the continuous phase of 1:1 mixture of two bioconjugated and dyed Janus droplets for 2 h. The fluorescence spectra indicate that all the COVID-19 patients’ serum samples have significantly higher levels of anti-SARS-CoV-2 spike IgG antibody than the control group (0 μg/mL) indicating the existence of anti-SARS-CoV-2 spike IgG antibody, which is consistent with the enzyme-linked immunosorbent assay (ELISA) results. In contrast, the SARS-CoV-2 negative samples, serum samples containing anti-Influenza IgG antibody, and serum samples containing anti-MERS-CoV spike antibody all show no statistical difference as compared with the control, indicating no anti-SARS-CoV-2 spike IgG antibody is detected in theses samples. The ELISA results for the negative samples and specificity panels are lower than 15 (cutoff) units and are determined as having no anti-SARS-CoV-2 spike IgG antibody in these serum samples, which is consistent with the agglutination assay results. The concentrations of anti-SARS-CoV-2 spike IgG antibody in sera are calculated from the relative fluorescence intensity at 580 nm and the correlation curve shown in Figure 4c. These results confirm that our agglutination detection assay has high sensitivity to the detection of anti-SARS-CoV-2 spike IgG antibody as well as good specificity in clinical samples (Table S2). Notably, both the sensitivity and specificity are 100%, which might be overestimating since our results are based on a limited number of tested samples. ELISA confirms that all the 10 COVID-19 patients’ serum samples have anti-SARS-CoV-2 spike IgG antibody (cut off value is 15 units) and the trend of the concentration of anti-SARS-CoV-2 spike IgG antibody detected by the top-read agglutination assay is similar to the data acquired from ELISA, which confirms the accuracy of our assay (Figure 7b).

Figure 7

Figure 7. Detection of anti-SARS-CoV-2 spike IgG antibody concentrations by top-read agglutination assay in clinical human serum samples from COVID-19 and normal patients. (a) Summary of concentrations of anti-SARS-CoV-2 spike IgG antibody detected in human sera from COVID-19 patients (P1 to P10), patients who are negative for SARS-CoV-2 (N1 to N5), patients who are negative for SARS-CoV-2 but have anti-influenza IgG antibody (Flu1 to Flu 3), and patients who are negative for SARS-CoV-2 but have anti-MERS-CoV spike IgG antibody (M1 to M3), by adding sera into the continuous phase of 1:1 mixture of Janus droplets containing of F-PBI dye in the fluorocarbon phase, and P-TCO and sub-PC dye in the hydrocarbon phase. Sample 0 μg/mL is the control with no addition of anti-SARS-CoV-2 spike IgG antibody or serum into the continuous phase of Janus droplets. All error bars are standard deviation calculated from three independent experiments (n = 3), and the asterisks (∗∗∗) represent statistical significance (***p ≤ 0.001). (b) Comparation of agglutination assay (black) and ELISA (blue) on the quantification of anti-SARS-CoV-2 spike IgG antibody in human sera from COVID-19 patients.

High Resolution Image
Download MS PowerPoint Slide

Conclusions

ARTICLE SECTIONS
Jump To
In summary, we report a sensitive, rapid and inexpensive method of detection of anti-SARS-CoV-2 spike IgG antibody, which could be used in diagnosis of the SARS-CoV-2 infection, by using Janus emulsions or Janus particles polymerized from Janus droplets as biosensors. These systems utilize secondary IgG antibody (Goat Anti-Human IgG antibody) and SARS-CoV-2 spike protein RBD to recognize and detect the anti-SARS-CoV-2 spike antibody. Mixtures of Janus emulsions coated separately with secondary IgG antibody or SARS-CoV-2 spike protein RBD are exposed to different concentrations of anti-SARS-CoV-2 spike antibody, and agglutination is observed at or above antibody concentrations of 0.2 μg/mL. We designed both top-down or bottom-up optical measurement methods for quantitatively measuring the concentration of antibody by using two pairs of dyes. Finally, we polymerized the Janus emulsions to increase the long-term stability of the assay materials. We find that these Janus particles could also be used for the biosensing of anti-SARS-CoV-2 spike antibody with similarly high sensitivity. The detection limits of our assay are sufficient for the detection of anti-SARS-CoV-2 spike antibody in real world samples, (46) which is proved by the agglutination experiment with serum samples from COVID-19 patients and normal patients. For some of the clinical samples that contain very high concentrations of anti-SARS-CoV-2 IgG, dilution might be needed before doing the measurements. As compared to the currently available serological test, our method demonstrates a new concept of tracking the tilting and formation of agglutination of Janus droplets or Janus particles for detection of the anti-SARS-CoV-2 spike IgG antibody levels in human sera with good sensitivity and specificity. Our method could rapidly detect the anti-SARS-CoV-2 spike IgG antibody level in 2 h with the LOD at 0.2 μg/mL without the requirement of expensive and complicated equipment. The inclusion of bottom-read scheme and polymerized droplet scheme largely improved the range of potential applications of our detection scheme, since the bottom-read scheme could minimize the influence of impurities in the liquid samples and the polymerized droplet scheme could improve the long-term stability of the droplets. Our system could not only be applied to the sensing of the anti-SARS-CoV-2 spike antibody but also can be extended to other antibodies or proteins in the future. For example, the method can be readily adapted to detect the anti-SARS-CoV-2 N protein antibody by conjugating the SARS-CoV-2 N protein to the Janus droplets and conducting an analogous assay for the detection of antibodies against the SARS-CoV-2 N protein. (47) The anti-SARS-CoV-2 IgM antibody which is a pentamer in serum is also an ideal analyte for our agglutination sensing schemes. (48) Overall, this biosensing method has considerable utility in the creation of future diverse bioassays.

Supporting Information

ARTICLE SECTIONS
Jump To

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acscentsci.1c00173.

  • Materials and instruments; experimental procedures; supplementary figures and tables (PDF)

Terms & Conditions

Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Author Information

ARTICLE SECTIONS
Jump To
  • Corresponding Author
  • Authors
    • Jie Li - Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    • Alberto Concellón - Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States;  Orcidhttps://orcid.org/0000-0002-8932-9085
    • Kosuke Yoshinaga - Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    • Zachary Nelson - Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States;  Orcidhttps://orcid.org/0000-0002-3949-682X
    • Qilin He - Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States;  Orcidhttps://orcid.org/0000-0002-3495-5265
  • Notes
    The authors declare no competing financial interest.

    A patent has been filed.

Acknowledgments

ARTICLE SECTIONS
Jump To

This research was supported by a Vannevar Bush Faculty Fellowship to TMS (Grant No. N000141812878). K.Y. thanks Funai Overseas Scholarship for financial support.

References

ARTICLE SECTIONS
Jump To

This article references 48 other publications.

  1. 1
    Fauci, A. S.; Lane, H. C.; Redfield, R. R. Covid-19 - Navigating the Uncharted. N. Engl. J. Med. 2020, 382 (13), 1268– 1269,  DOI: 10.1056/NEJMe2002387
    [Crossref], [PubMed], [CAS], Google Scholar
    1
    Covid-19 - navigating the uncharted
    Fauci, Anthony S.; Lane, H. Clifford; Redfield, Robert R.
    New England Journal of Medicine (2020), 382 (13), 1268-1269CODEN: NEJMAG; ISSN:1533-4406. (Massachusetts Medical Society)
    Achieving a better understanding of the pathogenesis of COVID-19 will be invaluable in navigating our responses in this uncharted area. Furthermore, genomic studies could delineate host factors that predispose persons to acquisition of infection and disease progression.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmt1WhsLk%253D&md5=70a891c20b085f5387abe9fee750ee15
  2. 2
    He, F.; Deng, Y.; Li, W. Coronavirus Disease 2019: What We Know?. J. Med. Virol. 2020, 92 (7), 719– 725,  DOI: 10.1002/jmv.25766
    [Crossref], [PubMed], [CAS], Google Scholar
    2
    Coronavirus disease 2019: What we know?
    He, Feng; Deng, Yu; Li, Weina
    Journal of Medical Virology (2020), 92 (7), 719-725CODEN: JMVIDB; ISSN:0146-6615. (Wiley-Blackwell)
    A review. In late Dec. 2019, a cluster of unexplained pneumonia cases has been reported in Wuhan, China. A few days later, the causative agent of this mysterious pneumonia was identified as a novel coronavirus. This causative virus has been temporarily named as severe acute respiratory syndrome coronavirus 2 and the relevant infected disease has been named as coronavirus disease 2019 (COVID-19) by the World Health Organization, resp. The COVID-19 epidemic is spreading in China and all over the world now. The purpose of this review is primarily to review the pathogen, clin. features, diagnosis, and treatment of COVID-19, but also to comment briefly on the epidemiol. and pathol. based on the current evidence.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXnsVWqtLc%253D&md5=4b071ade1e6bc6b8a70b2d389a93bc22
  3. 3
    Duan, K.; Liu, B.; Li, C.; Zhang, H.; Yu, T.; Qu, J.; Zhou, M.; Chen, L.; Meng, S.; Hu, Y. Effectiveness of Convalescent Plasma Therapy in Severe COVID-19 Patients. Proc. Natl. Acad. Sci. U. S. A. 2020, 117 (17), 9490– 9496,  DOI: 10.1073/pnas.2004168117
    [Crossref], [PubMed], [CAS], Google Scholar
    3
    Effectiveness of convalescent plasma therapy in severe COVID-19 patients
    Duan, Kai; Liu, Bende; Li, Cesheng; Zhang, Huajun; Yu, Ting; Qu, Jieming; Zhou, Min; Chen, Li; Meng, Shengli; Hu, Yong; Peng, Cheng; Yuan, Mingchao; Huang, Jinyan; Wang, Zejun; Yu, Jianhong; Gao, Xiaoxiao; Wang, Dan; Yu, Xiaoqi; Li, Li; Zhang, Jiayou; Wu, Xiao; Li, Bei; Xu, Yanping; Chen, Wei; Peng, Yan; Hu, Yeqin; Lin, Lianzhen; Liu, Xuefei; Huang, Shihe; Zhou, Zhijun; Zhang, Lianghao; Wang, Yue; Zhang, Zhi; Deng, Kun; Xia, Zhiwu; Gong, Qin; Zhang, Wei; Zheng, Xiaobei; Liu, Ying; Yang, Huichuan; Zhou, Dongbo; Yu, Ding; Hou, Jifeng; Shi, Zhengli; Chen, Saijuan; Chen, Zhu; Zhang, Xinxin; Yang, Xiaoming
    Proceedings of the National Academy of Sciences of the United States of America (2020), 117 (17), 9490-9496CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
    Currently,there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addn. to maximal supportive care and antiviral agents. The primary end-point was the safety of CP transfusion. The second endpoints were the improvement of clin. symptoms and lab. parameters within 3 days after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 days. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level(1:640). The clin. symptoms were significantly improved along with increase of oxyHb satn. within 3 days. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 x 109/L vs. 0.76 x 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiol. examns. showed varying degrees of absorption of lung lesions within 7 days. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were obsd. This study showed CP therapy was well tolerated and could potentially improve the clin. outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clin. benefit of CP therapy, needs further investigation in larger well-controlled trials.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXnvFeqt78%253D&md5=661598dff8a6351bcb7bec0ba7a4d92f
  4. 4
    Baden, L. R.; Rubin, E. J. Covid-19 - The Search for Effective Therapy. N. Engl. J. Med. 2020, 382 (19), 1851– 1852,  DOI: 10.1056/NEJMe2005477
    [Crossref], [PubMed], [CAS], Google Scholar
    4
    Covid-19 - The Search for Effective Therapy
    Baden Lindsey R; Rubin Eric J
    The New England journal of medicine (2020), 382 (19), 1851-1852 ISSN:.
    There is no expanded citation for this reference.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB383kvFOjtA%253D%253D&md5=d411b3055a2c404727eec0984e9aeb03
  5. 5
    Golchin, A.; Seyedjafari, E.; Ardeshirylajimi, A. Mesenchymal Stem Cell Therapy for COVID-19: Present or Future. Stem Cell Rev. Rep. 2020, 16 (3), 427– 433,  DOI: 10.1007/s12015-020-09973-w
    [Crossref], [PubMed], [CAS], Google Scholar
    5
    Mesenchymal Stem Cell Therapy for COVID-19: Present or Future
    Golchin, Ali; Seyedjafari, Ehsan; Ardeshirylajimi, Abdolreza
    Stem Cell Reviews and Reports (2020), 16 (3), 427-433CODEN: SCRREE; ISSN:2629-3277. (Springer)
    A review. Abstr.: "COVID-19" is the word that certainly isn't forgotten by everybody who lives in the first half of the twenty-first century. COVID-19, as a pandemic, has led many researchers from different biomedical fields to find solns. or treatments to manage the pandemic. However, no std. treatment for this disease has been discovered to date. Probably, preventing the severe acute respiratory infection form of COVID-19 as the most dangerous phase of this disease can be helpful for the treatment and redn. of the death rate. In this regard, mesenchymal stem cells (MSCs)-based immunomodulation treatment has been proposed as a suitable therapeutic approach and several clin. trials have begun. Recently, MSCs according to their immunomodulatory and regenerative properties attract attention in clin. trials. After the i.v. transplantation of MSCs, a significant population of cells accumulates in the lung, which they alongside immunomodulatory effect could protect alveolar epithelial cells, reclaim the pulmonary microenvironment, prevent pulmonary fibrosis, and cure lung dysfunction. Given the uncertainties in this area, we reviewed reported clin. trials and hypotheses to provide useful information to researchers and those interested in stem cell therapy. In this study, we considered this new approach to improve patient's immunol. responses to COVID-19 using MSCs and discussed the aspects of this proposed treatment. However, currently, there are no approved MSC-based approaches for the prevention and/or treatment of COVID-19 patients but clin. trials ongoing.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmvFWnu7w%253D&md5=cd3b1f6bcf37d6d9445bf4a38d1acedd
  6. 6
    Cantini, F.; Niccoli, L.; Matarrese, D.; Nicastri, E.; Stobbione, P.; Goletti, D. Baricitinib Therapy in COVID-19: A Pilot Study on Safety and Clinical Impact. J. Infect. 2020, 81 (2), 318– 356,  DOI: 10.1016/j.jinf.2020.04.017
    [Crossref], [PubMed], [CAS], Google Scholar
    6
    Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact
    Cantini, Fabrizio; Niccoli, Laura; Matarrese, Daniela; Nicastri, Emanuele; Stobbione, Paolo; Goletti, Delia
    Journal of Infection (2020), 81 (2), 318-356CODEN: JINFD2; ISSN:1532-2742. (Elsevier B.V.)
    Preliminary results on 12 patients with moderate COVID-19 pneumonia confirmed the safety of baricitinib therapy in a clin. context. In the baricitinib-treated group, all clin. characteristics and respiratory function parameters improved both at wk 1 and 2 compared to baseline. C-reactive protein values significantly decreased in the same timeframes. No infections, cardiovascular, and hematol. adverse events occurred after a 2 wk treatment.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVKkt7zO&md5=d47bb194919c10f50d24312f137ec88d
  7. 7
    Carfì, A.; Bernabei, R.; Landi, F.; Group, f. t. G. A. C.-P.-A. C. S. Persistent Symptoms in Patients After Acute COVID-19. JAMA 2020, 324 (6), 603– 605,  DOI: 10.1001/jama.2020.12603
    [Crossref], [PubMed], [CAS], Google Scholar
    7
    Persistent symptoms in patients after acute COVID-19
    Carfi, Angelo; Bernabei, Roberto; Landi, Francesco
    JAMA, the Journal of the American Medical Association (2020), 324 (6), 603-605CODEN: JAMAAP; ISSN:1538-3598. (American Medical Association)
    We assessed persistent symptoms in patients who were discharged from the hospital after recovery from COVID-19. Patients were assessed a mean of 60.3 days after onset of the 1st COVID-19 symptom. At the time of evaluation, only 18 (12.6%) were completely free of any COVID-19-related symptoms, while 32% had 1 or 2 symptoms and 55% had ≥3. None of the participants had fever or any signs or symptoms of acute illness. Worsened quality of life was obsd. among 44.1% of patients. A high proportion of individuals still reported fatigue (53.1%), dyspnea (43.4%), joint pain (27.3%), and chest pain (21.7%).
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs1SlsLfF&md5=d404441ba3f4ecf90c089c39b5107335
  8. 8
    Han, C.; Duan, C.; Zhang, S.; Spiegel, B.; Shi, H.; Wang, W.; Zhang, L.; Lin, R.; Liu, J.; Ding, Z. Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes. Am. J. Gastroenterol. 2020, 115 (6), 916– 923,  DOI: 10.14309/ajg.0000000000000664
    [Crossref], [PubMed], [CAS], Google Scholar
    8
    Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes
    Han Chaoqun; Duan Caihan; Zhang Shengyan; Shi Huiying; Wang Weijun; Zhang Lei; Lin Rong; Liu Jun; Ding Zhen; Hou Xiaohua; Spiegel Brennan
    The American journal of gastroenterology (2020), 115 (6), 916-923 ISSN:.
    OBJECTIVES: Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease. In this study, we sought to describe the clinical characteristics of COVID-19 patients with digestive symptoms and mild disease severity. METHODS: We identified COVID-19 patients with mild disease and one or more digestive symptoms (diarrhea, nausea, and vomiting), with or without respiratory symptoms, and compared them with a group presenting solely with respiratory symptoms. We followed up patients clinically until they tested negative for COVID-19 on at least 2 sequential respiratory tract specimens collected ≥24 hours apart. We then compared the clinical features between those with digestive symptoms and those with respiratory symptoms. RESULTS: There were 206 patients with low severity COVID-19, including 48 presenting with a digestive symptom alone, 69 with both digestive and respiratory symptoms, and 89 with respiratory symptoms alone. Between the 2 groups with digestive symptoms, 67 presented with diarrhea, of whom 19.4% experienced diarrhea as the first symptom in their illness course. The diarrhea lasted from 1 to 14 days, with an average duration of 5.4 ± 3.1 days and a frequency of 4.3 ± 2.2 bowel movements per day. Concurrent fever was found in 62.4% of patients with a digestive symptom. Patients with digestive symptoms presented for care later than those with respiratory symptoms (16.0 ± 7.7 vs 11.6 ± 5.1 days, P < 0.001). Nevertheless, patients with digestive symptoms had a longer duration between symptom onset and viral clearance (P < 0.001) and were more likely to be fecal virus positive (73.3% vs 14.3%, P = 0.033) than those with respiratory symptoms. DISCUSSION: We describe a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to have a longer delay before viral clearance, and to experience delayed diagnosis compared with patients with only respiratory symptoms.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38zmtlKmsg%253D%253D&md5=a8a5918e9e81d547aeac5e3ea3cea200
  9. 9
    Yan, C. H.; Faraji, F.; Prajapati, D. P.; Boone, C. E.; DeConde, A. S. Association of Chemosensory Dysfunction and COVID-19 in Patients Presenting with Influenza-like Symptoms. Int. Forum Allergy Rhinol. 2020, 10 (7), 806– 813,  DOI: 10.1002/alr.22579
    [Crossref], [PubMed], [CAS], Google Scholar
    9
    Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms
    Yan Carol H; Faraji Farhoud; Prajapati Divya P; DeConde Adam S; Prajapati Divya P; Boone Christine E
    International forum of allergy & rhinology (2020), 10 (7), 806-813 ISSN:.
    BACKGROUND: Rapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of coronavirus disease 2019 (COVID-19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID-19 may help facilitate screening and early isolation of cases. METHODS: A single-institution, cross-sectional study evaluating patient-reported symptoms with a focus on smell and taste was conducted using an internet-based platform on adult subjects who underwent testing for COVID-19. Logistic regression was employed to identify symptoms associated with COVID-19 positivity. RESULTS: A total of 1480 patients with influenza-like symptoms underwent COVID-19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID-19-positive patients and 203 of 1378 (15%) COVID-19-negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID-19-negative patients (p < 0.001). Smell and taste impairment were independently and strongly associated with COVID-19 positivity (anosmia: adjusted odds ratio [aOR] 10.9; 95% CI, 5.08-23.5; ageusia: aOR 10.2; 95% CI, 4.74-22.1), whereas sore throat was associated with COVID-19 negativity (aOR 0.23; 95% CI, 0.11-0.50). Of patients who reported COVID-19-associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness. CONCLUSION: In ambulatory individuals with influenza-like symptoms, chemosensory dysfunction was strongly associated with COVID-19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease-related symptoms.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38zktFCguw%253D%253D&md5=ffa5e8f95c6834fa5a14ebe51a3d0c32
  10. 10
    Mehta, P.; McAuley, D. F.; Brown, M.; Sanchez, E.; Tattersall, R. S.; Manson, J. J. U. K. COVID-19: Consider Cytokine Storm Syndromes and Immunosuppression. Lancet 2020, 395 (10229), 1033– 1034,  DOI: 10.1016/S0140-6736(20)30628-0
    [Crossref], [PubMed], [CAS], Google Scholar
    10
    COVID-19: consider cytokine storm syndromes and immunosuppression
    Mehta, Puja; McAuley, Daniel F.; Brown, Michael; Sanchez, Emilie; Tattersall, Rachel S.; Manson, Jessica J.
    Lancet (2020), 395 (10229), 1033-1034CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)
    All patients with severe COVID-19 should be screened for hyper-inflammation using lab. trends (e.g. increasing ferritin, decreasing platelet counts, or erythrocyte sedimentation rate) and the HScore to identify the subgroup of patients for whom immunosuppression could improve mortality. Therapeutic options include steroids, i.v. Ig, selective cytokine blockade (e.g. anakinra or tocilizumab) and JAK kinase inhibition.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXltFCjsb8%253D&md5=bd1ede3e6234aafcecf0547a3d768bfb
  11. 11
    Song, P.; Li, W.; Xie, J.; Hou, Y.; You, C. Cytokine Storm Induced by SARS-CoV-2. Clin. Chim. Acta 2020, 509, 280– 287,  DOI: 10.1016/j.cca.2020.06.017
    [Crossref], [PubMed], [CAS], Google Scholar
    11
    Cytokine storm induced by SARS-CoV-2
    Song, Peipei; Li, Wei; Xie, Jianqin; Hou, Yanlong; You, Chongge
    Clinica Chimica Acta (2020), 509 (), 280-287CODEN: CCATAR; ISSN:0009-8981. (Elsevier B.V.)
    A review. Coronavirus disease 2019 (COVID-19), caused by the virus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread widely throughout the world. Despite the strict global outbreak management and quarantine measures that have been implemented, the incidence of COVID-19 continues to rise, resulting in more than 290,000 deaths and representing an extremely serious threat to human life and health. The clin. symptoms of the affected patients are heterogeneous, ranging from mild upper respiratory symptoms to severe pneumonitis and even acute respiratory distress syndrome (ARDS) or death. Systemic immune over activation due to SARS-CoV-2 infection causes the cytokine storm, which is esp. noteworthy in severely ill patients with COVID-19. Pieces of evidence from current studies have shown that the cytokine storm may be an important factor in disease progression, even leading to multiple organ failure and death. This review provides an overview of the knowledge on the COVID-19 epidemiol. profile, the mol. mechanisms of the SARS-CoV-2-induced cytokine storm and immune responses, the pathophysiol. changes that occur during infection, the main antiviral compds. used in treatment strategies and the potential drugs for targeting cytokines, this information is presented to provide valuable guidance for further studies and for a therapeutic redn. of this excessive immune response.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlWns7%252FE&md5=cafd0380779103347d4867c3a893db38
  12. 12
    Thanh Le, T.; Andreadakis, Z.; Kumar, A.; Gómez Román, R.; Tollefsen, S.; Saville, M.; Mayhew, S. The COVID-19 Vaccine Development Landscape. Nat. Rev. Drug Discovery 2020, 19 (5), 305– 306,  DOI: 10.1038/d41573-020-00073-5
    [Crossref], [PubMed], [CAS], Google Scholar
    12
    The COVID-19 vaccine development landscape
    Thanh Le, Tung; Andreadakis, Zacharias; Kumar, Arun; Gomez Roman, Raul; Tollefsen, Stig; Saville, Melanie; Mayhew, Stephen
    Nature Reviews Drug Discovery (2020), 19 (5), 305-306CODEN: NRDDAG; ISSN:1474-1776. (Nature Research)
    A review on the development of vaccines for SARS-CoV-2. Topics include: the type of vaccines under development; the current stage of development; and the current no. of vaccine projects worldwide.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXnslOht7g%253D&md5=4be48c76fe66c0c69d24bebf2137eac3
  13. 13
    Graham, B. S. Rapid COVID-19 Caccine Development. Science 2020, 368 (6494), 945– 946,  DOI: 10.1126/science.abb8923
    [Crossref], [PubMed], [CAS], Google Scholar
    13
    Rapid COVID-19 vaccine development
    Graham, Barney S.
    Science (Washington, DC, United States) (2020), 368 (6494), 945-946CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)
    A review. Rapid development of a vaccine to prevent coronavirus disease 2019 (COVID-19) is a global imperative, and defining the stakes and potential hurdles is crit. because regulatory and medical decisions are based on benefit:risk calcns. The ability of viruses to achieve pandemic spread is diminished by establishing higher levels of community (herd) immunity, and a key question is whether protection against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) will happen by widespread deployment of an effective vaccine or by repeated waves of infection over the next few years until ∼60 to 70% of people develop immunity. Because the human population is naive to SARS-CoV-2, the consequences of repeated epidemics will be unacceptably high mortality, severe economic disruption, and major adjustments to our way of life. Therefore, the benefit of developing an effective vaccine is very high, and even greater if it can be deployed in time to prevent repeated or continuous epidemics.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVCntbnJ&md5=83023d5d1a0d88298e647c813eaf79f4
  14. 14
    Wu, S.-C. Progress and Concept for COVID-19 Vaccine Development. Biotechnol. J. 2020, 15 (6), e2000147– e2000147,  DOI: 10.1002/biot.202000147
    [Crossref], [PubMed], [CAS], Google Scholar
    14
    Progress and Concept for COVID-19 Vaccine Development
    Wu, Suh-Chin
    Biotechnology Journal (2020), 15 (6), 2000147CODEN: BJIOAM; ISSN:1860-6768. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review discussed the current status of coronavirus disease 2019 (COVID-19) vaccine development. Most vaccine candidates are based on the spike antigen either as inactivated vaccines, subunit vaccines, viral vectored vaccines, and nucleic acid-based DNA or mRNA vaccines.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXoslyhur4%253D&md5=d378e5bf153df53ce9bd860becacc98d
  15. 15
    Ibrahim, I. M.; Abdelmalek, D. H.; Elshahat, M. E.; Elfiky, A. A. COVID-19 Spike-Host Cell Receptor GRP78 Binding Site Prediction. J. Infect. 2020, 80 (5), 554– 562,  DOI: 10.1016/j.jinf.2020.02.026
    [Crossref], [PubMed], [CAS], Google Scholar
    15
    COVID-19 spike-host cell receptor GRP78 binding site prediction
    Ibrahim, Ibrahim M.; Abdelmalek, Doaa H.; Elshahat, Mohammed E.; Elfiky, Abdo A.
    Journal of Infection (2020), 80 (5), 554-562CODEN: JINFD2; ISSN:0163-4453. (Elsevier B.V.)
    Understanding the novel coronavirus (COVID-19) mode of host cell recognition may help to fight the disease and save lives. The spike protein of coronaviruses is the main driving force for host cell recognition. In this study, the COVID-19 spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined mol. modeling docking and structural bioinformatics. The COVID-19 spike protein is modeled using its counterpart, the SARS spike. Sequence and structural alignments show that 4 regions, in addn. to its cyclic nature have sequence and physicochem. similarities to the cyclic Pep42. Protein-protein docking was performed to test the 4 regions of the spike that fit tightly in the GRP78 Substrate Binding Domain β (SBDβ). The docking pose revealed the involvement of the SBDβ of GRP78 and the receptor-binding domain of the coronavirus spike protein in recognition of the host cell receptor. We reveal that the binding is more favorable between regions III (C391-C525) and IV (C480-C488) of the spike protein model and GRP78. Region IV is the main driving force for GRP78 binding with the predicted binding affinity of -9.8 kcal/mol. These 9 residues can be used to develop therapeutics specific against COVID-19.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVant7%252FJ&md5=d39d97ea95184f8f066318f63bb8dab1
  16. 16
    Du, L.; He, Y.; Zhou, Y.; Liu, S.; Zheng, B. J.; Jiang, S. The Spike Protein of SARS-CoV--a Target for Vaccine and Therapeutic Development. Nat. Rev. Microbiol. 2009, 7 (3), 226– 236,  DOI: 10.1038/nrmicro2090
    [Crossref], [PubMed], [CAS], Google Scholar
    16
    The spike protein of SARS-CoV - a target for vaccine and therapeutic development
    Du, Lanying; He, Yuxian; Zhou, Yusen; Liu, Shuwen; Zheng, Bo-Jian; Jiang, Shibo
    Nature Reviews Microbiology (2009), 7 (3), 226-236CODEN: NRMACK; ISSN:1740-1526. (Nature Publishing Group)
    A review. Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease caused by a novel coronavirus, SARS-coronavirus (SARS-CoV). The SARS-CoV spike (S) protein is composed of two subunits; the S1 subunit contains a receptor-binding domain that engages with the host cell receptor angiotensin-converting enzyme 2 and the S2 subunit mediates fusion between the viral and host cell membranes. The S protein plays key parts in the induction of neutralizing-antibody and T-cell responses, as well as protective immunity, during infection with SARS-CoV. In this Review, we highlight recent advances in the development of vaccines and therapeutics based on the S protein.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsFeqs7Y%253D&md5=610a46a8fed820bf5d0076e7c7d03c13
  17. 17
    Huang, Y.; Yang, C.; Xu, X.-F.; Xu, W.; Liu, S.-W. Structural and Functional Properties of SARS-CoV-2 Spike Protein: Potential Antivirus Drug Development for COVID-19. Acta Pharmacol. Sin. 2020, 41 (9), 1141– 1149,  DOI: 10.1038/s41401-020-0485-4
    [Crossref], [PubMed], [CAS], Google Scholar
    17
    Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19
    Huang Yuan; Yang Chan; Xu Xin-Feng; Xu Wei; Liu Shu-Wen; Liu Shu-Wen
    Acta pharmacologica Sinica (2020), 41 (9), 1141-1149 ISSN:.
    Coronavirus disease 2019 is a newly emerging infectious disease currently spreading across the world. It is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2, while the S2 subunit mediates viral cell membrane fusion by forming a six-helical bundle via the two-heptad repeat domain. In this review, we highlight recent research advance in the structure, function and development of antivirus drugs targeting the S protein.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38fgslensQ%253D%253D&md5=01c1cb2a20944318edd171a5869d2f84
  18. 18
    He, Y.; Zhou, Y.; Liu, S.; Kou, Z.; Li, W.; Farzan, M.; Jiang, S. Receptor-Binding Domain of SARS-CoV Spike Protein Induces Highly Potent Neutralizing Antibodies: Implication for Developing Subunit Vaccine. Biochem. Biophys. Res. Commun. 2004, 324 (2), 773– 781,  DOI: 10.1016/j.bbrc.2004.09.106
    [Crossref], [PubMed], [CAS], Google Scholar
    18
    Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine
    He, Yuxian; Zhou, Yusen; Liu, Shuwen; Kou, Zhihua; Li, Wenhui; Farzan, Michael; Jiang, Shibo
    Biochemical and Biophysical Research Communications (2004), 324 (2), 773-781CODEN: BBRCA9; ISSN:0006-291X. (Elsevier)
    The spike (S) protein of severe acute respiratory syndrome (SARS) coronavirus (CoV), a type I transmembrane envelope glycoprotein, consists of S1 and S2 domains responsible for virus binding and fusion, resp. The S1 contains a receptor-binding domain (RBD) that can specifically bind to angiotensin-converting enzyme 2 (ACE2), the receptor on target cells. Here the authors show that a recombinant fusion protein (designated RBD-Fc) contg. 193-amino acid RBD (residues 318-510) and a human IgG1 Fc fragment can induce highly potent antibody responses in the immunized rabbits. The antibodies recognized RBD on S1 domain and completely inhibited SARS-CoV infection at a serum diln. of 1:10,240. Rabbit antisera effectively blocked binding of S1, which contains RBD, to ACE2. This suggests that RBD can induce highly potent neutralizing antibody responses and has potential to be developed as an effective and safe subunit vaccine for prevention of SARS.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXotlCmsbo%253D&md5=a597ed0208b11c0af631fb72be5ee755
  19. 19
    Du, L.; Zhao, G.; He, Y.; Guo, Y.; Zheng, B.-J.; Jiang, S.; Zhou, Y. Receptor-Binding Domain of SARS-CoV Spike Protein Induces Long-Term Protective Immunity in An Animal Model. Vaccine 2007, 25 (15), 2832– 2838,  DOI: 10.1016/j.vaccine.2006.10.031
    [Crossref], [PubMed], [CAS], Google Scholar
    19
    Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model
    Du, Lanying; Zhao, Guangyu; He, Yuxian; Guo, Yan; Zheng, Bo-Jian; Jiang, Shibo; Zhou, Yusen
    Vaccine (2007), 25 (15), 2832-2838CODEN: VACCDE; ISSN:0264-410X. (Elsevier Ltd.)
    Development of effective vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is still a priority in prevention of re-emergence of SARS. Our previous studies have shown that the receptor-binding domain (RBD) of SARS-CoV spike (S) protein elicits highly potent neutralizing antibody responses in the immunized animals. But it is unknown whether RBD can also induce protective immunity in an animal model, a key aspect for vaccine development. In this study, BALB/c mice were vaccinated i.m. with 10 μg of RBD-Fc (RBD fused with human IgG1 Fc) and boosted twice at 3-wk intervals and one more time at 12th month. Humoral immune responses of vaccinated mice were investigated for up to 12 mo at a 1-mo interval and the neutralizing titers of produced antibodies were reported at months 0, 3, 6 and 12 post-vaccination. Mice were challenged with the homologous strain of SARS-CoV 5 days after the last boost, and sacrificed 5 days after the challenge. Mouse lung tissues were collected for detection of viral load, virus replication and histopathol. effects. Our results showed that RBD-Fc vaccination induced high titer of S-specific antibodies with long-term and potent SARS-CoV neutralizing activity. Four of five vaccinated mice were protected from subsequent SARS-CoV challenge because no significant virus replication, and no obvious histopathol. changes were found in the lung tissues of the vaccinated mice challenged with SARS-CoV. Only one vaccinated mouse had mild alveolar damage in the lung tissues. In contrast, high copies of SARS-CoV RNA and virus replication were detected, and pathol. changes were obsd. in the lung tissues of the control mice. In conclusion, our findings suggest that RBD, which can induce protective antibodies to SARS-CoV, may be further developed as a safe and effective SARS subunit vaccine.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXjtFGqtrY%253D&md5=a3d3a1bf9eaef5a1f1bcfd4c03b5b624
  20. 20
    Baker, A. N.; Richards, S.-J.; Guy, C. S.; Congdon, T. R.; Hasan, M.; Zwetsloot, A. J.; Gallo, A.; Lewandowski, J. R.; Stansfeld, P. J.; Straube, A. The SARS-COV-2 Spike Protein Binds Sialic Acids and Enables Rapid Detection in a Lateral Flow Point of Care Diagnostic Device. ACS Cent. Sci. 2020, 6 (11), 2046– 2052,  DOI: 10.1021/acscentsci.0c00855
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    20
    The SARS-COV-2 Spike Protein Binds Sialic Acids and Enables Rapid Detection in a Lateral Flow Point of Care Diagnostic Device
    Baker, Alexander N.; Richards, Sarah-Jane; Guy, Collette S.; Congdon, Thomas R.; Hasan, Muhammad; Zwetsloot, Alexander J.; Gallo, Angelo; Lewandowski, Jozef R.; Stansfeld, Phillip J.; Straube, Anne; Walker, Marc; Chessa, Simona; Pergolizzi, Giulia; Dedola, Simone; Field, Robert A.; Gibson, Matthew I.
    ACS Central Science (2020), 6 (11), 2046-2052CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)
    There is an urgent need to understand the behavior of the novel coronavirus (SARS-COV-2), which is the causative agent of COVID-19, and to develop point-of-care diagnostics. Here, a glyconanoparticle platform is used to discover that N-acetyl neuraminic acid has affinity toward the SARS-COV-2 spike glycoprotein, demonstrating its glycan-binding function. Optimization of the particle size and coating enabled detection of the spike glycoprotein in lateral flow and showed selectivity over the SARS-COV-1 spike protein. Using a virus-like particle and a pseudotyped lentivirus model, paper-based lateral flow detection was demonstrated in under 30 min, showing the potential of this system as a low-cost detection platform. The spike-protein from SARS-COV-2 is shown to bind sialic acids, which is exploited to assemble a lateral flow diagnostic tool, using glycans rather than antibodies, as the recognition unit.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVOlsbnP&md5=30a56fcd6d32e48834aa542773a21420
  21. 21
    Casalino, L.; Gaieb, Z.; Goldsmith, J. A.; Hjorth, C. K.; Dommer, A. C.; Harbison, A. M.; Fogarty, C. A.; Barros, E. P.; Taylor, B. C.; McLellan, J. S. Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein. ACS Cent. Sci. 2020, 6 (10), 1722– 1734,  DOI: 10.1021/acscentsci.0c01056
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    21
    Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein
    Casalino, Lorenzo; Gaieb, Zied; Goldsmith, Jory A.; Hjorth, Christy K.; Dommer, Abigail C.; Harbison, Aoife M.; Fogarty, Carl A.; Barros, Emilia P.; Taylor, Bryn C.; McLellan, Jason S.; Fadda, Elisa; Amaro, Rommie E.
    ACS Central Science (2020), 6 (10), 1722-1734CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)
    The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 28,000,000 infections and 900,000 deaths worldwide to date. Antibody development efforts mainly revolve around the extensively glycosylated SARS-CoV-2 spike (S) protein, which mediates host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2). Similar to many other viral fusion proteins, the SARS-CoV-2 spike utilizes a glycan shield to thwart the host immune response. Here, we built a full-length model of the glycosylated SARS-CoV-2 S protein, both in the open and closed states, augmenting the available structural and biol. data. Multiple microsecond-long, all-atom mol. dynamics simulations were used to provide an atomistic perspective on the roles of glycans and on the protein structure and dynamics. We reveal an essential structural role of N-glycans at sites N165 and N234 in modulating the conformational dynamics of the spike's receptor binding domain (RBD), which is responsible for ACE2 recognition. This finding is corroborated by biolayer interferometry expts., which show that deletion of these glycans through N165A and N234A mutations significantly reduces binding to ACE2 as a result of the RBD conformational shift toward the "down" state. Addnl., end-to-end accessibility analyses outline a complete overview of the vulnerabilities of the glycan shield of the SARS-CoV-2 S protein, which may be exploited in the therapeutic efforts targeting this mol. machine. Overall, this work presents hitherto unseen functional and structural insights into the SARS-CoV-2 S protein and its glycan coat, providing a strategy to control the conformational plasticity of the RBD that could be harnessed for vaccine development. The glycan shield is a sugary barrier that helps the viral SARS-CoV-2 spikes to evade the immune system. Beyond shielding, two of the spike's glycans are discovered to prime the virus for infection.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVOlsb3N&md5=52d499afcd7e3caa7d9e6017ffa86e45
  22. 22
    Xiang, F.; Wang, X.; He, X.; Peng, Z.; Yang, B.; Zhang, J.; Zhou, Q.; Ye, H.; Ma, Y.; Li, H. Antibody Detection and Dynamic Characteristics in Patients With Coronavirus Disease 2019. Clin. Infect. Dis. 2020, 71 (8), 1930– 1934,  DOI: 10.1093/cid/ciaa461
    [Crossref], [PubMed], [CAS], Google Scholar
    22
    Antibody detection and dynamic characteristics in patients with coronavirus disease 2019
    Xiang, Fei; Wang, Xiaorong; He, Xinliang; Peng, Zhenghong; Yang, Bohan; Zhang, Jianchu; Zhou, Qiong; Ye, Hong; Ma, Yanling; Li, Hui; Wei, Xiaoshan; Cai, Pengcheng; Ma, Wan-Li
    Clinical Infectious Diseases (2020), 71 (8), 1930-1934CODEN: CIDIEL; ISSN:1537-6591. (Oxford University Press)
    The coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been rapidly spreading nationwide and abroad. A serol. test to identify antibody dynamics and response to SARS-CoV-2 was developed. The antibodies against SARS-CoV-2 were detected by an ELISA based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold std. for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (rRT-PCR). The serodiagnostic power of the specific IgM and IgG antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, pos. predictive value (PPV), neg. predictive value (NPV), and consistency rate. The seroconversion of specific IgM and IgG antibodies were obsd. as early as the fourth day after symptom onset. In the patients with confirmed COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, resp., and those of IgG were 83.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9%. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, resp., and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 and rely on great specificity. The antibodies against SARS-CoV-2 can be detected in the middle and later stages of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as a complementary approach to viral nucleic acid assays.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisVWhtb%252FK&md5=c48e3aa8829f11a00738baa7ba157b67
  23. 23
    Zarzar, L. D.; Sresht, V.; Sletten, E. M.; Kalow, J. A.; Blankschtein, D.; Swager, T. M. Dynamically Reconfigurable Complex Emulsions Via Tunable Interfacial Tensions. Nature 2015, 518 (7540), 520– 524,  DOI: 10.1038/nature14168
    [Crossref], [PubMed], [CAS], Google Scholar
    23
    Dynamically reconfigurable complex emulsions via tunable interfacial tensions
    Zarzar, Lauren D.; Sresht, Vishnu; Sletten, Ellen M.; Kalow, Julia A.; Blankschtein, Daniel; Swager, Timothy M.
    Nature (London, United Kingdom) (2015), 518 (7540), 520-524CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)
    Emulsification is a powerful, well-known technique for mixing and dispersing immiscible components within a continuous liq. phase. Consequently, emulsions are central components of medicine, food and performance materials. Complex emulsions, including Janus droplets (i.e., droplets with faces of differing chemistries) and multiple emulsions, are of increasing importance in pharmaceuticals and medical diagnostics, in the fabrication of microparticles and capsules for food, in chem. sepns., in cosmetics, and in dynamic optics. Because complex emulsion properties and functions are related to the droplet geometry and compn., the development of rapid, simple fabrication approaches allowing precise control over the droplets' phys. and chem. characteristics is crit. Significant advances in the fabrication of complex emulsions have been made using a no. of procedures, ranging from large-scale, less precise techniques that give compositional heterogeneity using high-shear mixers and membranes, to small-vol. but more precise microfluidic methods. However, such approaches have yet to create droplet morphologies that can be controllably altered after emulsification. Reconfigurable complex liqs. potentially have great utility as dynamically tunable materials. Here we describe an approach to the one-step fabrication of three- and four-phase complex emulsions with highly controllable and reconfigurable morphologies. The fabrication makes use of the temp.-sensitive miscibility of hydrocarbon, silicone and fluorocarbon liqs., and is applied to both the microfluidic and the scalable batch prodn. of complex droplets. We demonstrate that droplet geometries can be alternated between encapsulated and Janus configurations by varying the interfacial tensions using hydrocarbon and fluorinated surfactants including stimuli-responsive and cleavable surfactants. This yields a generalizable strategy for the fabrication of multiphase emulsions with controllably reconfigurable morphologies and the potential to create a wide range of responsive materials.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXjsVagu70%253D&md5=6a36b3ea1d3721c03dc49e3d2766b733
  24. 24
    Zhang, W.; Liu, L. Study on the Formation and Properties of Liquid Crystal Emulsion in Cosmetic. J. Cosmet., Dermatol. Sci. Appl. 2013, 3 (2), 139– 144,  DOI: 10.4236/jcdsa.2013.32022
    [Crossref], [CAS], Google Scholar
    24
    Study on the formation and properties of liquid crystal emulsion in cosmetic
    Zhang, Wanping; Liu, Lingyan
    Journal of Cosmetics, Dermatological Sciences and Applications (2013), 3 (2), 139-144CODEN: JCDSEI; ISSN:2161-4512. (Scientific Research Publishing, Inc.)
    In this paper, the formation of liq. crystal structure in prepn. of emulsion and the change of those liq. crystal structures during storage and usage were studied. Besides, the rheol. and moisturizing property of the liq. crys- tal structure emulsion was investigated as well. The results show that the liq. crystal structure at oil-water interface in the emulsion forms gradually with cooling process after homogenization. The liq. crystal structure doesn't change significantly during the storage within 12 mo. And after emulsion being stored for 18 mo, the crystal structure starts to decomp. Upon application on the skin, the liq. crystal structure of emulsion was found to transform into other form with rubbing, although the liq. crystal structure still remains. The rheol. data shows that liq. crys- tal emulsion exhibits solid-like (elastic) property during storage, which is favorable for good stability. On the other hand, liq. crystal emulsion shows typical shear-thinning property upon usage, which leads to an excellent skin sensory feeling. And the improved moisturizing properties of such emulsion may be attributed to the liq. crystal structure.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXlvFOjsbY%253D&md5=b6ba825721d4ad73b6f153cc1598e454
  25. 25
    Masmoudi, H.; Dréau, Y. L.; Piccerelle, P.; Kister, J. The Evaluation of Cosmetic and Pharmaceutical Emulsions Aging Process using Classical Techniques and A New Method: FTIR. Int. J. Pharm. 2005, 289 (1), 117– 131,  DOI: 10.1016/j.ijpharm.2004.10.020
    [Crossref], [PubMed], [CAS], Google Scholar
    25
    The evaluation of cosmetic and pharmaceutical emulsions aging process using classical techniques and a new method: FTIR
    Masmoudi, H.; Le Dreau, Y.; Piccerelle, P.; Kister, J.
    International Journal of Pharmaceutics (2005), 289 (1-2), 117-131CODEN: IJPHDE; ISSN:0378-5173. (Elsevier B.V.)
    The purpose of this paper is to show how the utilization of Fourier Transform IR (FTIR) spectroscopy can be interesting in stability studying of cosmetic or pharmaceutical "oil in water" (O/W) emulsions. In this study temp. storage tests were performed to accelerate the aging process and evaluate the stability of five emulsions. Emulsions were analyzed by FTIR and classical methods (cond., viscosity, pH, texture anal.) in order to det. a method that would enable predicting the emulsion's stability. During the aging process, modifications of chem. functions are measured by FTIR (using spectrometric indexes), such modifications included: a decrease of unsatn. index, an increase of carbonyl index and a broadening of the carbonyl band. This band was deconvoluted to evaluate the contribution of different species in the broadening phenomenon, which seems to be caused by the appearance of free fatty acids. Conductimetry seems to be the most sensitive technique to assess phys. modifications during emulsion's aging. Concerning the most unstable emulsions, a progressive increasing of cond. was obsd. several months before the emulsion destabilizes. Consequently, FTIR and conductimetry are two complementary techniques. Conductimetry is a useful technique to predict emulsion destabilization while FTIR allows the measurement of chem. modifications and helps to understand the chem. mechanisms which occur during the oxidn.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXisFKjtg%253D%253D&md5=98e1f388771525c5242292b7dd4322e2
  26. 26
    Weinberg, G.; Ripper, R.; Feinstein, D. L.; Hoffman, W. Lipid Emulsion Infusion Rescues Dogs from Bupivacaine-Induced Cardiac Toxicity. Reg. Anesth. Pain Med. 2003, 28 (3), 198– 202,  DOI: 10.1097/00115550-200305000-00005
    [Crossref], [PubMed], [CAS], Google Scholar
    26
    Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity
    Weinberg, Guy; Ripper, Richard; Feinstein, Douglas L.; Hoffman, William
    Regional Anesthesia and Pain Medicine (2003), 28 (3), 198-202CODEN: RAPMFX; ISSN:1098-7339. (W. B. Saunders Co.)
    the authors previously demonstrated in rats that i.v. infusion of a lipid emulsion increases survival in resuscitation from severe bupivacaine cardiac toxicity. The present studies were undertaken to det. if this method is similarly effective in a non-rodent model using a larger animal. Bupivacaine, 10 mg/kg, was administered i.v. over 10 s to fasted dogs under isoflurane general anesthesia. Resuscitation included 10 min of internal cardiac massage followed with either saline or 20% lipid infusion, administered as a 4-mL/kg bolus followed by continuous infusion at 0.5 mL/kg/min for 10 min. ECG, arterial blood pressure (BP), and myocardial pH (pHm) and pO2 (pmO2) were continuously measured. Survival after 10 min of unsuccessful cardiac massage was successful for all lipid-treated dogs (n = 6), but with no survivors in the saline controls (n = 6) (P <.01). Hemodynamics, PmO2, and pHm were improved during resuscitation with lipid compared with saline treatment in which dogs did not recover. the authors found that infusing a lipid emulsion during resuscitation from bupivacaine-induced cardiac toxicity substantially improved hemodynamics, pmO2, and pHm and increased survival in dogs.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXkt1yjsL8%253D&md5=d97d8e79e2f4da5333610accccf967c1
  27. 27
    Cave, G.; Harvey, M. Intravenous Lipid Emulsion as Antidote Beyond Local Anesthetic Toxicity: A Systematic Review. Acad. Emerg. Med. 2009, 16 (9), 815– 824,  DOI: 10.1111/j.1553-2712.2009.00499.x
    [Crossref], [PubMed], [CAS], Google Scholar
    27
    Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a systematic review
    Cave Grant; Harvey Martyn
    Academic emergency medicine : official journal of the Society for Academic Emergency Medicine (2009), 16 (9), 815-24 ISSN:.
    OBJECTIVES: The objective was to asses the efficacy of lipid emulsion as antidotal therapy outside the accepted setting of local anesthetic toxicity. METHODS: Literature was accessed through PubMed, OVID (1966-February 2009), and EMBASE (1947-February 2009) using the search terms "intravenous" AND ["fat emulsion" OR "lipid emulsion" OR "Intralipid"] AND ["toxicity" OR "resuscitation" OR "rescue" OR "arrest" OR "antidote"]. Additional author and conference publication searches were undertaken. Publications describing the use of lipid emulsion as antidotal treatment in animals or humans were included. RESULTS: Fourteen animal studies, one human study, and four case reports were identified. In animal models, intravenous lipid emulsion (ILE) has resulted in amelioration of toxicity associated with cyclic antidepressants, verapamil, propranolol, and thiopentone. Administration in human cases has resulted in successful resuscitation from combined bupropion/lamotrigine-induced cardiac arrest, reversal of sertraline/quetiapine-induced coma, and amelioration of verapamil- and beta blocker-induced shock. CONCLUSIONS: Management of overdose with highly lipophilic cardiotoxic medications should proceed in accord with established antidotal guidelines and early poisons center consultation. Data from animal experiments and human cases are limited, but suggestive that ILE may be helpful in potentially lethal cardiotoxicity or developed cardiac arrest attributable to such agents. Use of lipid emulsion as antidote remains a nascent field warranting further preclinical study and systematic reporting of human cases of use.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1Mjgs12gtw%253D%253D&md5=7072e687cc8d6316e29c3967d2a6acf8
  28. 28
    Lu, T.; Spruijt, E. Multiphase Complex Coacervate Droplets. J. Am. Chem. Soc. 2020, 142 (6), 2905– 2914,  DOI: 10.1021/jacs.9b11468
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    28
    Multiphase complex coacervate droplets
    Lu, Tiemei; Spruijt, Evan
    Journal of the American Chemical Society (2020), 142 (6), 2905-2914CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    Liq.-liq. phase sepn. plays an important role in cellular organization. Many subcellular condensed bodies are hierarchically organized into multiple coexisting domains or layers. However, our mol. understanding of the assembly and internal organization of these multicomponent droplets is still incomplete, and rules for the coexistence of condensed phases are lacking. Here, we show that the formation of hierarchically organized multiphase droplets with up to three coexisting layers is a generic phenomenon in mixts. of complex coacervates, which serve as models of charge-driven liq.-liq. phase sepd. systems. We present simple theor. guidelines to explain both the hierarchical arrangement and the demixing transition in multiphase droplets using the interfacial tensions and crit. salt concn. as inputs. Multiple coacervates can coexist if they differ sufficiently in macromol. d., and we show that the assocd. differences in crit. salt concn. can be used to predict multiphase droplet formation. We also show that the coexisting coacervates present distinct chem. environments that can conc. guest mols. to different extents. Our findings suggest that condensate immiscibility may be a very general feature in biol. systems, which could be exploited to design self-organized synthetic compartments to control biomol. processes.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXht1Crtbs%253D&md5=8cdc7926ce612f24ee2adafc0339394c
  29. 29
    Galus, S.; Kadzińska, J. Food Applications of Emulsion-Based Edible Films and Coatings. Trends Food Sci. Technol. 2015, 45 (2), 273– 283,  DOI: 10.1016/j.tifs.2015.07.011
    [Crossref], [CAS], Google Scholar
    29
    Food applications of emulsion-based edible films and coatings
    Galus, Sabina; Kadzinska, Justyna
    Trends in Food Science & Technology (2015), 45 (2), 273-283CODEN: TFTEEH; ISSN:0924-2244. (Elsevier Ltd.)
    A review. An increasing awareness among consumers regarding the healthy lifestyle have prompted research on novel techniques of prolonging the shelf life of food products without the necessity of using preservatives. Thanks to their ability to improve global food quality, edible films and coatings have been particularly considered in food preservation. Changing mech. and barrier properties depending on the main component in the biopolymer matrix caused an increasing interest in composite structures, which enable to explore the complementary advantages of each component as well as to minimize their disadvantages.This review discusses the potential food applications of emulsified edible films and coatings. The materials, prepn. methods, and phys. properties are also presented. Lipids are usually added to edible films and coatings to impart hydrophobicity and thereby reduce moisture loss. A very wide range of lipid components is available including natural waxes, resins, acetoglycerides, fatty acids, and petroleum-based, mineral and vegetable oils. The emulsification process of the lipid phase in the aq. phase is necessary prior to the coating application.Emulsion-based edible films and coatings find application in fresh and processed food products, fruits and vegetables, cheeses, meat, sausages and bakery products. Composite emulsion-based edible materials produced from hydrocolloids and lipids result in better functionality than films produced with one component, esp. with respect to their water barrier properties. In general, more research is needed to improve application processes of emulsion-based edible materials, esp. sensory aspects, to be appropriate for each product.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXht1Sns7%252FL&md5=58d1cf76c6c6cb9e0c02914a2dc82e93
  30. 30
    Tavernier, I.; Wijaya, W.; Van der Meeren, P.; Dewettinck, K.; Patel, A. R. Food-Grade Particles for Emulsion Stabilization. Trends Food Sci. Technol. 2016, 50, 159– 174,  DOI: 10.1016/j.tifs.2016.01.023
    [Crossref], [CAS], Google Scholar
    30
    Food-grade particles for emulsion stabilization
    Tavernier, Iris; Wijaya, Wahyu; Van der Meeren, Paul; Dewettinck, Koen; Patel, Ashok R.
    Trends in Food Science & Technology (2016), 50 (), 159-174CODEN: TFTEEH; ISSN:0924-2244. (Elsevier Ltd.)
    The use of solid, food-grade particles as emulsion stabilizers is highly promising in the field of food science and technol. Food-grade particles (e.g. fat and wax crystals, protein particles, and protein-polysaccharide complexes) can form alternatives to inorg. particles (e.g. silica, alumina or clays), which are incompatible and mostly unserviceable when considering food and nutraceutical applications. This review provides a concise insight into the concept of Pickering stabilization with the emphasis on the available food-grade particles that have been researched in this field. The innovative food applications of particle-stabilized emulsions are also discussed.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitlSgu78%253D&md5=30b5730cb594cd78850ae5f95dd74d28
  31. 31
    Lee, D.; Weitz, D. A. Double Emulsion-Templated Nanoparticle Colloidosomes with Selective Permeability. Adv. Mater. 2008, 20 (18), 3498– 3503,  DOI: 10.1002/adma.200800918
    [Crossref], [CAS], Google Scholar
    31
    Double emulsion-templated nanoparticle colloidosomes with selective permeability
    Lee, Daeyeon; Weitz, David A.
    Advanced Materials (Weinheim, Germany) (2008), 20 (18), 3498-3503CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)
    Nanoparticle colloidosomes, shown in the SEM image, are generated by using water-in-oil-in-water double emulsions as templates. Hydrophobic silica nanoparticles that are dispersed in the oil phase stabilize the double emulsions, and subsequently become the shell of the colloidosomes upon removal of the org. solvent as shown in the figure.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXht1SgtbvF&md5=4bed920b6c55ef3aa5b191311ce03abe
  32. 32
    Bouyer, E.; Mekhloufi, G.; Rosilio, V.; Grossiord, J.-L.; Agnely, F. Proteins, Polysaccharides, and Their Complexes Used as Stabilizers for Emulsions: Alternatives to Synthetic Surfactants in the Pharmaceutical Field?. Int. J. Pharm. 2012, 436 (1), 359– 378,  DOI: 10.1016/j.ijpharm.2012.06.052
    [Crossref], [PubMed], [CAS], Google Scholar
    32
    Proteins, polysaccharides, and their complexes used as stabilizers for emulsions: Alternatives to synthetic surfactants in the pharmaceutical field?
    Bouyer, Eleonore; Mekhloufi, Ghozlene; Rosilio, Veronique; Grossiord, Jean-Louis; Agnely, Florence
    International Journal of Pharmaceutics (Amsterdam, Netherlands) (2012), 436 (1-2), 359-378CODEN: IJPHDE; ISSN:0378-5173. (Elsevier B.V.)
    A review. Emulsions are widely used in pharmaceutics for the encapsulation, solubilization, entrapment, and controlled delivery of active ingredients. In order to answer the increasing demand for clean label excipients, natural polymers can replace the potentially irritative synthetic surfactants used in emulsion formulation. Indeed, biopolymers are currently used in the food industry to stabilize emulsions, and they appear as promising candidates in the pharmaceutical field too. All proteins and some polysaccharides are able to adsorb at a globule surface, thus decreasing the interfacial tension and enhancing the interfacial elasticity. However, most polysaccharides stabilize emulsions simply by increasing the viscosity of the continuous phase. Proteins and polysaccharides may also be assocd. either through covalent bonding or electrostatic interactions. The combination of the properties of these biopolymers under appropriate conditions leads to increased emulsion stability. Alternative layers of oppositely charged biopolymers can also be formed around the globules to obtain multi-layered "membranes". These layers can provide electrostatic and steric stabilization thus improving thermal stability and resistance to external treatment. The novel biopolymer-stabilized emulsions have a great potential in the pharmaceutical field for encapsulation, controlled digestion, and targeted release although several challenging issues such as storage and bacteriol. concerns still need to be addressed.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht12jsbzI&md5=8c296ebb85fc2d35399d0f1ac7b1dc9c
  33. 33
    Sadurní, N.; Solans, C.; Azemar, N.; García-Celma, M. J. Studies on the Formation of O/W Nano-Emulsions, by Low-Energy Emulsification Methods, Suitable for Pharmaceutical Applications. Eur. J. Pharm. Sci. 2005, 26 (5), 438– 445,  DOI: 10.1016/j.ejps.2005.08.001
    [Crossref], [PubMed], [CAS], Google Scholar
    33
    Studies on the formation of O/W nano-emulsions, by low-energy emulsification methods, suitable for pharmaceutical applications
    Sadurni, Nuria; Solans, Conxita; Azemar, Nuria; Garcia-Celma, Maria Jose
    European Journal of Pharmaceutical Sciences (2005), 26 (5), 438-445CODEN: EPSCED; ISSN:0928-0987. (Elsevier B.V.)
    The formation of O/W nano-emulsions suitable for pharmaceutical application and the solubilization of a practically non-water-sol. drug, lidocaine, were studied in water/non-ionic surfactant/oil systems. Nano-emulsions were prepd. by low-energy emulsification methods, changing the compn. at const. temp. Kinetic stability was assessed by measuring droplet diam. as a function of time. Lidocaine solubilization was studied in nano-emulsions with high water content. In the water/Cremophor EL/Miglyol 812 system the lowest droplet sizes, from 14 to 39 nm at 10/90 and 40/60 oil/surfactant ratios, resp., and 90% of water content, were obtained with an emulsification method consisting of stepwise addn. of water to oil/surfactant mixts. at 70 °C. Nano-emulsions of this system showed high kinetic stability. Droplet diams. did not exceed 67 nm after a period of at least 7 mo. The max. lidocaine concn. solubilized in nano-emulsions of the water/Cremophor EL/Miglyol 812 system with 90 and 95% of water content was 3.5 and 2.1%, resp. These values are within the therapeutic range of lidocaine.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtFKns7rJ&md5=83ca304ada6773bbd988dccc958ea2ff
  34. 34
    Li, J.; Savagatrup, S.; Nelson, Z.; Yoshinaga, K.; Swager, T. M. Fluorescent Janus Emulsions for Biosensing of Listeria Monocytogenes. Proc. Natl. Acad. Sci. U. S. A. 2020, 117 (22), 11923– 11930,  DOI: 10.1073/pnas.2002623117
    [Crossref], [PubMed], [CAS], Google Scholar
    34
    Fluorescent Janus emulsions for biosensing of Listeria monocytogenes
    Li, Jie; Savagatrup, Suchol; Nelson, Zachary; Yoshinaga, Kosuke; Swager, Timothy M.
    Proceedings of the National Academy of Sciences of the United States of America (2020), 117 (22), 11923-11930CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
    Here we report a sensing method for Listeria monocytogenes based on the agglutination of all-liq. Janus emulsions. This two-dye assay enables the rapid detection of trace Listeria in less than 2 h via an emissive signal produced in response to Listeria binding. The biorecognition interface between the Janus emulsions is assembled by attaching antibodies to a functional surfactant polymer with a tetrazine/transcyclooctene click reaction. The strong binding between Listeria and the Listeria antibody located at the hydrocarbon surface of the emulsions results in the tilting of the Janus structure from its equil. position to produce emission that would ordinarily be obscured by a blocking dye. This method provides rapid and inexpensive Listeria detection with high sensitivity (<100 CFU/mL in 2 h) that can be paired with many antibody or related recognition elements to create a new class of biosensors.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlSlsbvO&md5=f8648a76e23585f89f234acf99ee7166
  35. 35
    Zentner, C. A.; Anson, F.; Thayumanavan, S.; Swager, T. M. Dynamic Imine Chemistry at Complex Double Emulsion Interfaces. J. Am. Chem. Soc. 2019, 141 (45), 18048– 18055,  DOI: 10.1021/jacs.9b06852
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    35
    Dynamic Imine Chemistry at Complex Double Emulsion Interfaces
    Zentner, Cassandra A.; Anson, Francesca; Thayumanavan, S.; Swager, Timothy M.
    Journal of the American Chemical Society (2019), 141 (45), 18048-18055CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    Interfacial chem. provides an opportunity to control dynamic materials. By harnessing the dynamic covalent nature of imine bonds, emulsions are generated in situ, predictably manipulated, and ultimately destroyed along liq.-liq. and emulsion-solid interfaces through simple perturbation of the imine equil. We report the rapid prodn. of surfactants and double emulsions through spontaneous in situ imine formation at the liq.-liq. interface of oil/water. Complex double emulsions with imine surfactants are stable to neutral and basic conditions and display dynamic behavior with acid-catalyzed hydrolysis and imine exchange. We demonstrate the potential of in situ imine surfactant formation to generate complex surfactants with biomols. (i.e., antibodies) for biosensing applications. Furthermore, imine formation at the emulsion-solid interface offers a triggered payload release mechanism. Our results illustrate how simple, dynamic interfacial imine formation can translate changes in bonding to macroscopic outputs.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitVKqsbvM&md5=72c669fb6d4faef199a392479fed257f
  36. 36
    Zeininger, L.; Nagelberg, S.; Harvey, K. S.; Savagatrup, S.; Herbert, M. B.; Yoshinaga, K.; Capobianco, J. A.; Kolle, M.; Swager, T. M. Rapid Detection of Salmonella enterica via Directional Emission from Carbohydrate-Functionalized Dynamic Double Emulsions. ACS Cent. Sci. 2019, 5 (5), 789– 795,  DOI: 10.1021/acscentsci.9b00059
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    36
    Rapid Detection of Salmonella enterica via Directional Emission from Carbohydrate-Functionalized Dynamic Double Emulsions
    Zeininger, Lukas; Nagelberg, Sara; Harvey, Kent S.; Savagatrup, Suchol; Herbert, Myles B.; Yoshinaga, Kosuke; Capobianco, Joseph A.; Kolle, Mathias; Swager, Timothy M.
    ACS Central Science (2019), 5 (5), 789-795CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)
    Reliable early-stage detection of foodborne pathogens is a global public health challenge that requires new and improved sensing strategies. Here, we demonstrate that dynamically reconfigurable fluorescent double emulsions can function as highly responsive optical sensors for the rapid detection of carbohydrates fructose, glucose, mannose, and mannan, which are involved in many biol. and pathogenic phenomena. The proposed detection strategy relies on reversible reactions between boronic acid surfactants and carbohydrates at the hydrocarbon/water interface leading to a dynamic reconfiguration of the droplet morphol., which alters the angular distribution of the droplet's fluorescent light emission. We exploit this unique chem.-morphol.-optical coupling to detect Salmonella enterica, a type of bacteria with a well-known binding affinity for mannose. We further demonstrate an oriented immobilization of antibodies at the droplet interface to permit higher selectivity. Our demonstrations yield a new, inexpensive, robust, and generalizable sensing strategy that can help to facilitate the early detection of foodborne pathogens.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXnvFCgs74%253D&md5=e62cfeb041c416f28ded00bff23beb13
  37. 37
    Zhang, Q.; Savagatrup, S.; Kaplonek, P.; Seeberger, P. H.; Swager, T. M. Janus Emulsions for the Detection of Bacteria. ACS Cent. Sci. 2017, 3 (4), 309– 313,  DOI: 10.1021/acscentsci.7b00021
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    37
    Janus Emulsions for the Detection of Bacteria
    Zhang, Qifan; Savagatrup, Suchol; Kaplonek, Paulina; Seeberger, Peter H.; Swager, Timothy M.
    ACS Central Science (2017), 3 (4), 309-313CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)
    Janus emulsion assays that rely on carbohydrate-lectin binding for the detection of Escherichia coli bacteria are described. Surfactants contg. mannose are self-assembled at the surface of Janus droplets to produce particles with lectin binding sites. Janus droplets orient in a vertical direction as a result of the difference in densities between the hydrocarbon and fluorocarbon solvents. Binding of lectin to mannose(s) causes agglutination and a tilted geometry. The distinct optical difference between naturally aligned and agglutinated Janus droplets produces signals that can be detected quant. The Janus emulsion assay sensitively and selectively binds to E. coli at 104 cfu/mL and can be easily prepd. with long-time stability. It provides the basis for the development of inexpensive portable devices for fast, on-site pathogen detection.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXks1OhsLg%253D&md5=a2f0a9d8e087ee399313d1b9a13a43b8
  38. 38
    Zhang, Q.; Zeininger, L.; Sung, K.-J.; Miller, E. A.; Yoshinaga, K.; Sikes, H. D.; Swager, T. M. Emulsion Agglutination Assay for the Detection of Protein–Protein Interactions: An Optical Sensor for Zika Virus. ACS Sens. 2019, 4 (1), 180– 184,  DOI: 10.1021/acssensors.8b01202
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    38
    Emulsion Agglutination Assay for the Detection of Protein-Protein Interactions: An Optical Sensor for Zika Virus
    Zhang, Qifan; Zeininger, Lukas; Sung, Ki-Joo; Miller, Eric A.; Yoshinaga, Kosuke; Sikes, Hadley D.; Swager, Timothy M.
    ACS Sensors (2019), 4 (1), 180-184CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)
    A new class of Janus emulsion agglutination assay is reported for the detection of interfacial protein-protein interactions. Janus emulsion droplets are functionalized with a thermally stable, antigen binding protein rcSso7d variant (rcSso7d-ZNS1) for the detection of Zika NS1 protein. The emulsion droplets contg. fluorescent dyes in their hydrocarbon and fluorocarbon phases intensify the intrinsic optical signal with the emission intensity ratio, which can be detected by a simple optical fiber. This assay provides an opportunity for the in-field detection of Zika virus and other pathogens with a stable, inexpensive, and convenient device.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXkvFaktw%253D%253D&md5=5fd06764372cdf3e3c526b8a32bfd586
  39. 39
    Zarzar, L. D.; Kalow, J. A.; He, X.; Walish, J. J.; Swager, T. M. Optical Visualization and Quantification of Enzyme Activity Using Dynamic Droplet Lenses. Proc. Natl. Acad. Sci. U. S. A. 2017, 114 (15), 3821– 3825,  DOI: 10.1073/pnas.1618807114
    [Crossref], [PubMed], [CAS], Google Scholar
    39
    Optical visualization and quantification of enzyme activity using dynamic droplet lenses
    Zarzar, Lauren D.; Kalow, Julia A.; He, Xinping; Walish, Joseph J.; Swager, Timothy M.
    Proceedings of the National Academy of Sciences of the United States of America (2017), 114 (15), 3821-3825CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
    In this paper, we describe an approach to measuring enzyme activity based on the reconfiguration of complex emulsions. Changes in the morphol. of these complex emulsions, driven by enzyme-responsive surfactants, modulate the transmission of light through a sample. Through this method we demonstrate how simple photodetector measurements may be used to monitor enzyme kinetics. This approach is validated by quant. measurements of enzyme activity for three different classes of enzymes (amylase, lipase, and sulfatase), relying on two distinct mechanisms for coupling droplet morphol. to enzyme activity (host-guest interactions with uncaging and mol. cleavage).
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXkvF2itLs%253D&md5=506744cf1dbee9a57eb93780bc58eb53
  40. 40
    Nagelberg, S.; Zarzar, L. D.; Nicolas, N.; Subramanian, K.; Kalow, J. A.; Sresht, V.; Blankschtein, D.; Barbastathis, G.; Kreysing, M.; Swager, T. M. Reconfigurable and Responsive Droplet-Based Compound Micro-Lenses. Nat. Commun. 2017, 8 (1), 14673,  DOI: 10.1038/ncomms14673
    [Crossref], [PubMed], [CAS], Google Scholar
    40
    Reconfigurable and responsive droplet-based compound micro-lenses
    Nagelberg Sara; Nicolas Natalie; Barbastathis George; Kolle Mathias; Zarzar Lauren D; Kalow Julia A; Swager Timothy M; Zarzar Lauren D; Subramanian Kaushikaram; Kreysing Moritz; Kalow Julia A; Sresht Vishnu; Blankschtein Daniel
    Nature communications (2017), 8 (), 14673 ISSN:.
    Micro-scale optical components play a crucial role in imaging and display technology, biosensing, beam shaping, optical switching, wavefront-analysis, and device miniaturization. Herein, we demonstrate liquid compound micro-lenses with dynamically tunable focal lengths. We employ bi-phase emulsion droplets fabricated from immiscible hydrocarbon and fluorocarbon liquids to form responsive micro-lenses that can be reconfigured to focus or scatter light, form real or virtual images, and display variable focal lengths. Experimental demonstrations of dynamic refractive control are complemented by theoretical analysis and wave-optical modelling. Additionally, we provide evidence of the micro-lenses' functionality for two potential applications-integral micro-scale imaging devices and light field display technology-thereby demonstrating both the fundamental characteristics and the promising opportunities for fluid-based dynamic refractive micro-scale compound lenses.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1czjsFSlug%253D%253D&md5=d719553a97e3326fd82b7a33f8f70a78
  41. 41
    van Oss, C. J.; Good, R. J.; Chaudhury, M. K. Nature of the Antigen-Antibody Interaction: Primary and Secondary Bonds: Optimal Conditions for Association and Dissociation. J. Chromatogr., Biomed. Appl. 1986, 376, 111– 119,  DOI: 10.1016/S0378-4347(00)80828-2
    [Crossref], [CAS], Google Scholar
    41
    Nature of the antigen-antibody interaction. Primary and secondary bonds: optimal conditions for association and dissociation
    Van Oss, C. J.; Good, R. J.; Chaudhury, M. K.
    Journal of Chromatography, Biomedical Applications (1986), 376 (), 111-19CODEN: JCBADL; ISSN:0378-4347.
    A review with 22 refs. discussing antigen-antibody bonds including (i) coulombic bonds, (ii) Ca2+ bridges, (iii) H-bonds, (iv) Lifshitz-van der Waals bonds, and (v) hydrophobic interactions.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL28Xkt1amur0%253D&md5=3f67e5e4e7fc2cd6fd5d7967fa0c827c
  42. 42
    Taylor, M. T.; Blackman, M. L.; Dmitrenko, O.; Fox, J. M. Design and Synthesis of Highly Reactive Dienophiles for the Tetrazine–trans-Cyclooctene Ligation. J. Am. Chem. Soc. 2011, 133 (25), 9646– 9649,  DOI: 10.1021/ja201844c
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    42
    Design and Synthesis of Highly Reactive Dienophiles for the Tetrazine-trans-Cyclooctene Ligation
    Taylor, Michael T.; Blackman, Melissa L.; Dmitrenko, Olga; Fox, Joseph M.
    Journal of the American Chemical Society (2011), 133 (25), 9646-9649CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    Computation was used to design a trans-cyclooctene deriv. that displays enhanced reactivity in the tetrazine-trans-cycloctene ligation. The optimized deriv. is an (E)-bicyclo[6.1.0]non-4-ene with a cis-ring fusion, in which the eight-membered ring is forced to adopt a highly strained half-chair' conformation. Toward 3,6-dipyridyl-s-tetrazine in MeOH at 25 °C, the strained deriv. is 19 and 27 times more reactive than the parent trans-cyclooctene and 4E-cyclooct-4-enol, resp. Toward 3,6-diphenyl-s-tetrazine in MeOH at 25°C, the strained deriv. is 160 times more reactive than the parent trans-cyclooctene.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXntVenu7Y%253D&md5=3eb79dbda8c538c9a37f77e2a83b0ac5
  43. 43
    Stephanopoulos, N.; Francis, M. B. Choosing An Effective Protein Bioconjugation Strategy. Nat. Chem. Biol. 2011, 7 (12), 876– 884,  DOI: 10.1038/nchembio.720
    [Crossref], [PubMed], [CAS], Google Scholar
    43
    Choosing an effective protein bioconjugation strategy
    Stephanopoulos, Nicholas; Francis, Matthew B.
    Nature Chemical Biology (2011), 7 (12), 876-884CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)
    A review. The collection of chem. techniques that can be used to attach synthetic groups to proteins has expanded substantially in recent years. Each of these approaches allows new protein targets to be addressed, leading to advances in biol. understanding, new protein-drug conjugates, targeted medical imaging agents and hybrid materials with complex functions. The protein modification reactions in current use vary widely in their inherent site selectivity, overall yields and functional group compatibility. Some are more amenable to large-scale bioconjugate prodn., and a no. of techniques can be used to label a single protein in a complex biol. mixt. This review examines the way in which exptl. circumstances influence one's selection of an appropriate protein modification strategy. It also provides a simple decision tree that can narrow down the possibilities in many instances. The review concludes with example studies that examine how this decision process has been applied in different contexts.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVOisbbP&md5=f635776ca8c147f5e2e1227f8eec29d8
  44. 44
    Czuban, M.; Srinivasan, S.; Yee, N. A.; Agustin, E.; Koliszak, A.; Miller, E.; Khan, I.; Quinones, I.; Noory, H.; Motola, C. Bio-Orthogonal Chemistry and Reloadable Biomaterial Enable Local Activation of Antibiotic Prodrugs and Enhance Treatments against Staphylococcus aureus Infections. ACS Cent. Sci. 2018, 4 (12), 1624– 1632,  DOI: 10.1021/acscentsci.8b00344
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    44
    Bio-Orthogonal Chemistry and Reloadable Biomaterial Enable Local Activation of Antibiotic Prodrugs and Enhance Treatments against Staphylococcus aureus Infections
    Czuban, Magdalena; Srinivasan, Sangeetha; Yee, Nathan A.; Agustin, Edgar; Koliszak, Anna; Miller, Ethan; Khan, Irfan; Quinones, Ilenis; Noory, Hasina; Motola, Christopher; Volkmer, Rudolf; Di Luca, Mariagrazia; Trampuz, Andrej; Royzen, Maksim; Mejia Oneto, Jose M.
    ACS Central Science (2018), 4 (12), 1624-1632CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)
    Systemic administration of antibiotics can cause severe side-effects such as liver and kidney toxicity, destruction of healthy gut bacteria, as well as multidrug resistance. Here, we present a bio-orthogonal chem.-based strategy toward local prodrug concn. and activation. The strategy is based on the inverse electron-demand Diels-Alder chem. between trans-cyclooctene and tetrazine and involves a biomaterial that can conc. and activate multiple doses of systemic antibiotic therapy prodrugs at a local site. We demonstrate that a biomaterial, consisting of alginate hydrogel modified with tetrazine, is efficient at activating multiple doses of prodrugs of vancomycin and daptomycin in vitro as well as in vivo. These results support a drug delivery process that is independent of endogenous environmental markers. This approach is expected to improve therapeutic efficacy with decreased side-effects of antibiotics against bacterial infections. The platform has a wide scope of possible applications such as wound healing, and cancer and immunotherapy.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXisVynsrbE&md5=cdbcf2a406c85c4e195e1c763bd33718
  45. 45
    Yoshinaga, K.; Swager, T. M. Fluorofluorescent Perylene Bisimides. Synlett 2018, 29 (19), 2509– 2514,  DOI: 10.1055/s-0037-1610224
    [Crossref], [CAS], Google Scholar
    45
    Fluorofluorescent Perylene Bisimides
    Yoshinaga, Kosuke; Swager, Timothy M.
    Synlett (2018), 29 (19), 2509-2514CODEN: SYNLES; ISSN:0936-5214. (Georg Thieme Verlag)
    Perfluorinated liqs. can exhibit immiscibility with org. solvents and water, and provide orthogonal opportunities in chem. Examples of emissive dyes that display only fluorous phase soly. are limited, despite the many potential applications. Perylene bisimides are among the most versatile dyes and are known for their outstanding stability and high quantum yields. Herein, we report the synthesis of two new "fluorofluorescent" perylene bisimide dyes, designed to be sol. in the fluorous phases. These two dyes possess unique photophys. properties, including dramatic increases in fluorescence quantum yields when treated with Bronsted acids as well as aggregation in the fluorous phase.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVWqtb3N&md5=f5e06c5dbb8d3e8d0e7a59b168a21c71
  46. 46
    Ibarrondo, F. J.; Fulcher, J. A.; Goodman-Meza, D.; Elliott, J.; Hofmann, C.; Hausner, M. A.; Ferbas, K. G.; Tobin, N. H.; Aldrovandi, G. M.; Yang, O. O. Rapid Decay of Anti-SARS-CoV-2 Antibodies in Persons with Mild Covid-19. N. Engl. J. Med. 2020, 383 (11), 1085– 1087,  DOI: 10.1056/NEJMc2025179
    [Crossref], [PubMed], [CAS], Google Scholar
    46
    Rapid Decay of Anti-SARS-CoV-2 Antibodies in Persons with Mild Covid-19
    Ibarrondo F Javier; Fulcher Jennifer A; Goodman-Meza David; Elliott Julie; Hofmann Christian; Hausner Mary A; Ferbas Kathie G; Tobin Nicole H; Aldrovandi Grace M; Yang Otto O
    The New England journal of medicine (2020), 383 (11), 1085-1087 ISSN:.
    There is no expanded citation for this reference.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38jms1OitA%253D%253D&md5=f6ec1343ea3984738792517b9b38ac90
  47. 47
    Dutta, N. K.; Mazumdar, K.; Gordy, J. T. The Nucleocapsid Protein of SARS-CoV-2: A Target for Vaccine Development. J. Virol. 2020, 94 (13), e00647– 00620,  DOI: 10.1128/JVI.00647-20
    [Crossref], [PubMed], [CAS], Google Scholar
    47
    The nucleocapsid protein of SARS-CoV-2: a target for vaccine development
    Dutta, Noton K.; Mazumdar, Kaushiki; Gordy, James T.
    Journal of Virology (2020), 94 (13), e00647-20CODEN: JOVIAM; ISSN:1098-5514. (American Society for Microbiology)
    A review. During the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there has been an un-precedented level of global collaboration that has led to a rapid characterization of SARS-CoV-2. New reports have addnl. shown that the crystal structure of the SARS-CoV-2 nucleocapsid protein is similar to those of previously described coronavirus N proteins, but their surface electrostatic potential characteristics are distinct. In this issue, Cong et al. (17) used a mouse hepatitis virus (MHV)model to show that the viral nucleocapsid (N) protein contributes to forming helical ribonucleoproteins during the packaging of the RNA genome, regulating viral RNA syn-thesis during replication and transcription and modulating metab. in infected subjects. This study complements others that have shown N to have multiple functions (25). It is becoming more evident just how crit. this protein is for multiple steps of the viral lifecycle. These reports offer important and timely insights relevant to the SARS-CoV-2 N protein, a vaccine target that has some distinct advantages over other potential SARS-CoV-2 antigen.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVKhu73I&md5=c237f78bec48e79eea76c871cdea4e5e
  48. 48
    Czajkowsky, D. M.; Shao, Z. The Human IgM Pentamer is A Mushroom-Shaped Molecule with A Flexural Bias. Proc. Natl. Acad. Sci. U. S. A. 2009, 106 (35), 14960– 14965,  DOI: 10.1073/pnas.0903805106
    [Crossref], [PubMed], [CAS], Google Scholar
    48
    The human IgM pentamer is a mushroom-shaped molecule with a flexural bias
    Czajkowsky, Daniel M.; Shao, Zhifeng
    Proceedings of the National Academy of Sciences of the United States of America (2009), 106 (35), 14960-14965, S14960/1-S14960/4CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
    The textbook planar model of pentameric IgM, a potent activator of complement C1q, is based upon the crystallog. structure of IgG. Although widely accepted, key predictions of this model have not yet been directly confirmed, which is particularly important since IgG lacks a major Ig fold domain in its Fc region that is present in IgM. Here, the authors construct a homol.-based structural model of the IgM pentamer using the recently obtained crystallog. structure of IgE Fc, which has this addnl. Ig domain, under the constraint that all of the cysteine residues known to form disulfide bridges both within each monomer and between monomers are bonded together. In contrast to the planar model, this model predicts a non-planar, mushroom-shaped complex, with the central portion formed by the C-terminal domains protruding out of the plane formed by the Fab domains. This unexpected conformation of IgM is, however, directly confirmed by cryo-at. force microscopy of individual human IgM mols. Further anal. of this model with free energy calcns. of out-of-plane Fab domain rotations reveals a pronounced asymmetry favoring flexions toward the central protrusion. This bias, together with polyvalent attachment to cell surface antigen, would ensure that the IgM pentamer is oriented on the cell membrane with its C1q binding sites fully exposed to the soln., and thus provides a mechanistic explanation for the first steps of C1q activation by IgM.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtFGnurrN&md5=aacabfc918d4057d13302c3eb140a4d1

Cited By

This article is cited by 19 publications.

  1. Tyler J. Durkin, Baishali Barua, Jamie J. Holmstrom, Vasiliki Karanikola, Suchol Savagatrup. Functionalized Amphiphilic Block Copolymers and Complex Emulsions for Selective Sensing of Dissolved Metals at Liquid–Liquid Interfaces. Langmuir 2023, 39 (36) , 12845-12854. https://doi.org/10.1021/acs.langmuir.3c01761
  2. Cooper P. Thome, Wren S. Hoertdoerfer, Julia R. Bendorf, Jin Gyun Lee, C. Wyatt Shields, IV. Electrokinetic Active Particles for Motion-Based Biomolecule Detection. Nano Letters 2023, 23 (6) , 2379-2387. https://doi.org/10.1021/acs.nanolett.3c00319
  3. Vivian Trinh, Cameron S. Malloy, Tyler J. Durkin, Aakanksha Gadh, Suchol Savagatrup. Detection of PFAS and Fluorinated Surfactants Using Differential Behaviors at Interfaces of Complex Droplets. ACS Sensors 2022, 7 (5) , 1514-1523. https://doi.org/10.1021/acssensors.2c00257
  4. Qilin He, Harikrishnan Vijayamohanan, Jie Li, Timothy M. Swager. Multifunctional Photonic Janus Particles. Journal of the American Chemical Society 2022, 144 (12) , 5661-5667. https://doi.org/10.1021/jacs.2c01787
  5. Vidhishri Kesarwani, Julia A. Walker, Edward C. Henderson, Gabriel Huynh, Heather McLiesh, Maryza Graham, Megan Wieringa, Mark M. Banaszak Holl, Gil Garnier, Simon R. Corrie. Column Agglutination Assay Using Polystyrene Microbeads for Rapid Detection of Antibodies against SARS-CoV-2. ACS Applied Materials & Interfaces 2022, 14 (2) , 2501-2509. https://doi.org/10.1021/acsami.1c17859
  6. Baishali Barua, Tyler J. Durkin, Isabel M. Beeley, Aakanksha Gadh, Suchol Savagatrup. Multiplexed and continuous microfluidic sensors using dynamic complex droplets. Soft Matter 2023, 19 (10) , 1930-1940. https://doi.org/10.1039/D3SM00074E
  7. Tyler J. Durkin, Baishali Barua, Suchol Savagatrup. Modification of amphiphilic block copolymers for responsive and biologically active surfactants in complex droplets. Giant 2023, 13 , 100134. https://doi.org/10.1016/j.giant.2022.100134
  8. Freddy A. Nunez, Ana C. H. Castro, Isabela P. Daher, Edecio Cunha-Neto, Jorge Kalil, Silvia B. Boscardin, Alexandre J. C. Lanfredi, Vivian L. de Oliveira, Wendel A. Alves. ZnO-Based Electrochemical Immunosensor to Assess Vaccine-Induced Antibody-Mediated Immunity against Wild-Type and Gamma SARS-CoV-2 Strains. Biosensors 2023, 13 (3) , 371. https://doi.org/10.3390/bios13030371
  9. Pablo Simón Marqués, Martyna Krajewska, Bradley D. Frank, Krystyna Prochaska, Lukas Zeininger. Morphology‐Dependent Aggregation‐Induced Emission of Janus Emulsion Surfactants. Chemistry – A European Journal 2023, 8 https://doi.org/10.1002/chem.202203790
  10. Srushti Karadkar, Abhishekh Tiwari, Atul Changdev Chaskar. Recent advancements in Janus nanoparticle-based biosensing platforms. International Nano Letters 2022, 20 https://doi.org/10.1007/s40089-022-00385-x
  11. Mengqi Ye, Haixia Zhang, Zongxu Wu, Chenguang Ding, Zhijie Jin, Fang Wang, He Bian. Supercritical carbon dioxide microemulsion stabilized with zwitterionic surfactant: A dissipative particle dynamics simulation study. Journal of Molecular Liquids 2022, 363 , 119863. https://doi.org/10.1016/j.molliq.2022.119863
  12. Sulaiman Alsalameh, Khalid Alnajjar, Tariq Makhzoum, Noor Al Eman, Ismail Shakir, Tanveer Ahmad Mir, Khaled Alkattan, Raja Chinnappan, Ahmed Yaqinuddin. Advances in Biosensing Technologies for Diagnosis of COVID-19. Biosensors 2022, 12 (10) , 898. https://doi.org/10.3390/bios12100898
  13. Chenguang Ding, Lingling Ge, Rong Guo. Anisotropic droplets with uniform internal structure prepared in batch-scale by combination of vortex mixing and phase separation. Journal of Molecular Liquids 2022, 361 , 119616. https://doi.org/10.1016/j.molliq.2022.119616
  14. Yuhan Wang, Peixuan Zhao, Shihao Zhang, Kexiao Zhu, Xiaoya Shangguan, Lishang Liu, Shusheng Zhang. Application of Janus Particles in Point-of-Care Testing. Biosensors 2022, 12 (9) , 689. https://doi.org/10.3390/bios12090689
  15. Haixia Zhang, Lingling Ge, Rong Guo. Responsive emulsions with Janus topology constructed by magneto-surfactants and remote control of emulsion stability. JCIS Open 2022, 5 , 100043. https://doi.org/10.1016/j.jciso.2022.100043
  16. Gregor Lang, Carolin Grill, Thomas Scheibel. Seitenspezifische Funktionalisierung von Janusfasern aus rekombinanter Spinnenseide. Angewandte Chemie 2022, 134 (11) https://doi.org/10.1002/ange.202115232
  17. Gregor Lang, Carolin Grill, Thomas Scheibel. Site‐Specific Functionalization of Recombinant Spider Silk Janus Fibers. Angewandte Chemie International Edition 2022, 61 (11) https://doi.org/10.1002/anie.202115232
  18. Wei Li, Daodao Hu, Jinxin Ma, Shukun Shen. Amphiphilic Janus Microspheres Prepared by Caged Photoactivatable Alkoxysilane. Coatings 2022, 12 (2) , 198. https://doi.org/10.3390/coatings12020198
  19. Beatriz Jurado-Sánchez, Susana Campuzano, José M. Pingarrón, Alberto Escarpa. Janus particles and motors: unrivaled devices for mastering (bio)sensing. Microchimica Acta 2021, 188 (12) https://doi.org/10.1007/s00604-021-05053-z
Download PDF

  • Abstract

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 1

    Figure 1. General scheme for interfacial bioconjugation of the Janus droplets’ hydrocarbon phase. (a) Chemical structure of polymer P-TCO. (b) Bioconjugation scheme of Tetrazine Goat Anti-Human IgG antibody and Tetrazine-SARS-CoV-2 spike protein receptor binding domain (RBD) to P-TCO at the hydrocarbon–water interface of Janus droplets. (c) Optical image of 1:1 mixture of P-TCO polydisperse Janus droplets after bioconjugation with SARS-CoV-2 spike RBD and P-TCO Janus droplets after bioconjugation with Goat Anti-Human IgG antibody. Scale bar = 50 μm.

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 2

    Figure 2. Agglutination assay achieved by adding anti-SARS-CoV-2 spike IgG antibody into the continuous phase of the mixture of Janus droplets. (a) Agglutination scheme with the addition of anti-SARS-CoV-2 spike antibody. (b) Bright field microscope image of a 1:1 mixture of Goat Anti-Human IgG antibody and SARS-CoV-2 spike protein RBD bioconjugated monodispersed droplets, 2 h after the addition of 60 μg/mL anti-SARS-CoV-2 spike antibody. The scatter light of the agglutinated droplets appears as dark objects. (c) The same assay as in panel b, but with 1 μg/mL anti-SARS-CoV-2 spike antibody. Scale bar = 50 μm.

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 3

    Figure 3. Illustration of the agglutination assay with Janus droplets containing blocker dye sub-PC in the hydrocarbon phase and emissive dye F-PBI in the fluorocarbon phase. (a) Scheme of a P-TCO functionalized Janus droplet with a blocker sub-PC dye in the hydrocarbon phase and the F-PBI red emissive dye in the fluorocarbon phase. (b) Agglutination scheme with the two-dye system. (c) Optical microscope image of the fully bioconjugated monodispersed droplets (1:1 mixture) that also contain the two dyes showing their aligned state without the addition of anti-SARS-CoV-2 spike antibody. (d) Optical microscope image of the same 1:1 mixture as in part c, but with the addition of anti-SARS-CoV-2 spike antibody at a concentration of 20 μg/mL after 2 h. Scale bar = 50 μm.

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 4

    Figure 4. Quantification of agglutination assay by measuring the fluorescence spectra. (a) Schematic of excitation and detection of fluorescence from the naturally oriented or agglutinated dye containing emulsions. Light is only able to reach the red dye when the droplets are tilted in the agglutinated structure. (b) Fluorescence spectra (λex = 361 nm) of 1:1 mixture of dye containing fully bioconjugated Janus droplets with the addition of anti-SARS-CoV-2 spike antibody at different concentrations. Note that the fluorescence intensity increases with concentration. (c) Correlation of concentration of anti-SARS-CoV-2 spike antibody and relative fluorescence intensity at 580 nm. All error bars are standard deviation calculated from three independent experiments (n = 3), and the asterisks (∗∗) represent statistical significance (**p ≤ 0.01).

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 5

    Figure 5. Illustrations of Janus droplets containing emissive Lumogen F Orange 240 dye in the hydrocarbon phase and blocker dye F-BHQ in the fluorocarbon phase and agglutination quantification. (a) A Janus droplet having an emissive perylene dye (Lumogen F Orange 240) in the hydrocarbon phase and a nonemissive dye (F-BHQ) in the fluorocarbon phase. (b) Optical image of Lumogen F Orange 240 in DEB and F-BHQ in HFE7500 under normal or UV light. (c) Bottom excitation and detection scheme of Janus droplets containing F-BHQ and Lumogen F Orange 240. (d) Fluorescence spectra (λex = 400 nm) of a 1:1 mixture of bioconjugated Janus droplets containing of F-BHQ dye in the fluorocarbon phase, P-TCO, and Lumogen F Orange 240 dye in the hydrocarbon phase, after the addition of anti-SARS-CoV-2 spike antibody at different concentrations. (e) Correlation of concentration of anti-SARS-CoV-2 spike antibody and relative fluorescence intensity at 535 nm. All error bars are standard deviations calculated from three independent experiments (n = 3), and the asterisks (∗∗) represent statistical significance (**p ≤ 0.01).

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 6

    Figure 6. Polymerization of Janus droplets to form Janus particles. (a) Schematic illustration of the polymerization of Janus droplets and their agglutination. (b) Optical image of Janus particles before the addition of anti-SARS-CoV-2 spike antibody. Scale bar = 50 μm. (c) Optical image of 1:1 mixture of Janus particles 2 h after the addition of 20 μg/mL of anti-SARS-CoV-2 spike antibody. The red circles on the image signify the agglutinations of Janus particles. Note that some minor agglutinations are not circled to minimize clutter in the image. Scale bar = 50 μm. (d) SEM image of Janus particles after polymerization. (e) Fluorescence spectra (λex = 361 nm) of particles containing of F-PBI dye in the fluorocarbon phase, P-TCO, and sub-PC dye in the hydrocarbon phase, after addition of anti-SARS-CoV-2 spike antibody at different concentrations. (f) Correlation of concentration of anti-SARS-CoV-2 spike antibody and relative fluorescence intensity at 588 nm. All error bars are standard deviation calculated from three independent experiments (n = 3), the asterisks (∗∗) represent statistical significance (**p ≤ 0.01).

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 7

    Figure 7. Detection of anti-SARS-CoV-2 spike IgG antibody concentrations by top-read agglutination assay in clinical human serum samples from COVID-19 and normal patients. (a) Summary of concentrations of anti-SARS-CoV-2 spike IgG antibody detected in human sera from COVID-19 patients (P1 to P10), patients who are negative for SARS-CoV-2 (N1 to N5), patients who are negative for SARS-CoV-2 but have anti-influenza IgG antibody (Flu1 to Flu 3), and patients who are negative for SARS-CoV-2 but have anti-MERS-CoV spike IgG antibody (M1 to M3), by adding sera into the continuous phase of 1:1 mixture of Janus droplets containing of F-PBI dye in the fluorocarbon phase, and P-TCO and sub-PC dye in the hydrocarbon phase. Sample 0 μg/mL is the control with no addition of anti-SARS-CoV-2 spike IgG antibody or serum into the continuous phase of Janus droplets. All error bars are standard deviation calculated from three independent experiments (n = 3), and the asterisks (∗∗∗) represent statistical significance (***p ≤ 0.001). (b) Comparation of agglutination assay (black) and ELISA (blue) on the quantification of anti-SARS-CoV-2 spike IgG antibody in human sera from COVID-19 patients.

    High Resolution Image
    Download MS PowerPoint Slide

  • References

    ARTICLE SECTIONS
    Jump To

    This article references 48 other publications.

    1. 1
      Fauci, A. S.; Lane, H. C.; Redfield, R. R. Covid-19 - Navigating the Uncharted. N. Engl. J. Med. 2020, 382 (13), 1268– 1269,  DOI: 10.1056/NEJMe2002387
      [Crossref], [PubMed], [CAS], Google Scholar
      1
      Covid-19 - navigating the uncharted
      Fauci, Anthony S.; Lane, H. Clifford; Redfield, Robert R.
      New England Journal of Medicine (2020), 382 (13), 1268-1269CODEN: NEJMAG; ISSN:1533-4406. (Massachusetts Medical Society)
      Achieving a better understanding of the pathogenesis of COVID-19 will be invaluable in navigating our responses in this uncharted area. Furthermore, genomic studies could delineate host factors that predispose persons to acquisition of infection and disease progression.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmt1WhsLk%253D&md5=70a891c20b085f5387abe9fee750ee15
    2. 2
      He, F.; Deng, Y.; Li, W. Coronavirus Disease 2019: What We Know?. J. Med. Virol. 2020, 92 (7), 719– 725,  DOI: 10.1002/jmv.25766
      [Crossref], [PubMed], [CAS], Google Scholar
      2
      Coronavirus disease 2019: What we know?
      He, Feng; Deng, Yu; Li, Weina
      Journal of Medical Virology (2020), 92 (7), 719-725CODEN: JMVIDB; ISSN:0146-6615. (Wiley-Blackwell)
      A review. In late Dec. 2019, a cluster of unexplained pneumonia cases has been reported in Wuhan, China. A few days later, the causative agent of this mysterious pneumonia was identified as a novel coronavirus. This causative virus has been temporarily named as severe acute respiratory syndrome coronavirus 2 and the relevant infected disease has been named as coronavirus disease 2019 (COVID-19) by the World Health Organization, resp. The COVID-19 epidemic is spreading in China and all over the world now. The purpose of this review is primarily to review the pathogen, clin. features, diagnosis, and treatment of COVID-19, but also to comment briefly on the epidemiol. and pathol. based on the current evidence.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXnsVWqtLc%253D&md5=4b071ade1e6bc6b8a70b2d389a93bc22
    3. 3
      Duan, K.; Liu, B.; Li, C.; Zhang, H.; Yu, T.; Qu, J.; Zhou, M.; Chen, L.; Meng, S.; Hu, Y. Effectiveness of Convalescent Plasma Therapy in Severe COVID-19 Patients. Proc. Natl. Acad. Sci. U. S. A. 2020, 117 (17), 9490– 9496,  DOI: 10.1073/pnas.2004168117
      [Crossref], [PubMed], [CAS], Google Scholar
      3
      Effectiveness of convalescent plasma therapy in severe COVID-19 patients
      Duan, Kai; Liu, Bende; Li, Cesheng; Zhang, Huajun; Yu, Ting; Qu, Jieming; Zhou, Min; Chen, Li; Meng, Shengli; Hu, Yong; Peng, Cheng; Yuan, Mingchao; Huang, Jinyan; Wang, Zejun; Yu, Jianhong; Gao, Xiaoxiao; Wang, Dan; Yu, Xiaoqi; Li, Li; Zhang, Jiayou; Wu, Xiao; Li, Bei; Xu, Yanping; Chen, Wei; Peng, Yan; Hu, Yeqin; Lin, Lianzhen; Liu, Xuefei; Huang, Shihe; Zhou, Zhijun; Zhang, Lianghao; Wang, Yue; Zhang, Zhi; Deng, Kun; Xia, Zhiwu; Gong, Qin; Zhang, Wei; Zheng, Xiaobei; Liu, Ying; Yang, Huichuan; Zhou, Dongbo; Yu, Ding; Hou, Jifeng; Shi, Zhengli; Chen, Saijuan; Chen, Zhu; Zhang, Xinxin; Yang, Xiaoming
      Proceedings of the National Academy of Sciences of the United States of America (2020), 117 (17), 9490-9496CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
      Currently,there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addn. to maximal supportive care and antiviral agents. The primary end-point was the safety of CP transfusion. The second endpoints were the improvement of clin. symptoms and lab. parameters within 3 days after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 days. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level(1:640). The clin. symptoms were significantly improved along with increase of oxyHb satn. within 3 days. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 x 109/L vs. 0.76 x 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiol. examns. showed varying degrees of absorption of lung lesions within 7 days. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were obsd. This study showed CP therapy was well tolerated and could potentially improve the clin. outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clin. benefit of CP therapy, needs further investigation in larger well-controlled trials.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXnvFeqt78%253D&md5=661598dff8a6351bcb7bec0ba7a4d92f
    4. 4
      Baden, L. R.; Rubin, E. J. Covid-19 - The Search for Effective Therapy. N. Engl. J. Med. 2020, 382 (19), 1851– 1852,  DOI: 10.1056/NEJMe2005477
      [Crossref], [PubMed], [CAS], Google Scholar
      4
      Covid-19 - The Search for Effective Therapy
      Baden Lindsey R; Rubin Eric J
      The New England journal of medicine (2020), 382 (19), 1851-1852 ISSN:.
      There is no expanded citation for this reference.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB383kvFOjtA%253D%253D&md5=d411b3055a2c404727eec0984e9aeb03
    5. 5
      Golchin, A.; Seyedjafari, E.; Ardeshirylajimi, A. Mesenchymal Stem Cell Therapy for COVID-19: Present or Future. Stem Cell Rev. Rep. 2020, 16 (3), 427– 433,  DOI: 10.1007/s12015-020-09973-w
      [Crossref], [PubMed], [CAS], Google Scholar
      5
      Mesenchymal Stem Cell Therapy for COVID-19: Present or Future
      Golchin, Ali; Seyedjafari, Ehsan; Ardeshirylajimi, Abdolreza
      Stem Cell Reviews and Reports (2020), 16 (3), 427-433CODEN: SCRREE; ISSN:2629-3277. (Springer)
      A review. Abstr.: "COVID-19" is the word that certainly isn't forgotten by everybody who lives in the first half of the twenty-first century. COVID-19, as a pandemic, has led many researchers from different biomedical fields to find solns. or treatments to manage the pandemic. However, no std. treatment for this disease has been discovered to date. Probably, preventing the severe acute respiratory infection form of COVID-19 as the most dangerous phase of this disease can be helpful for the treatment and redn. of the death rate. In this regard, mesenchymal stem cells (MSCs)-based immunomodulation treatment has been proposed as a suitable therapeutic approach and several clin. trials have begun. Recently, MSCs according to their immunomodulatory and regenerative properties attract attention in clin. trials. After the i.v. transplantation of MSCs, a significant population of cells accumulates in the lung, which they alongside immunomodulatory effect could protect alveolar epithelial cells, reclaim the pulmonary microenvironment, prevent pulmonary fibrosis, and cure lung dysfunction. Given the uncertainties in this area, we reviewed reported clin. trials and hypotheses to provide useful information to researchers and those interested in stem cell therapy. In this study, we considered this new approach to improve patient's immunol. responses to COVID-19 using MSCs and discussed the aspects of this proposed treatment. However, currently, there are no approved MSC-based approaches for the prevention and/or treatment of COVID-19 patients but clin. trials ongoing.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmvFWnu7w%253D&md5=cd3b1f6bcf37d6d9445bf4a38d1acedd
    6. 6
      Cantini, F.; Niccoli, L.; Matarrese, D.; Nicastri, E.; Stobbione, P.; Goletti, D. Baricitinib Therapy in COVID-19: A Pilot Study on Safety and Clinical Impact. J. Infect. 2020, 81 (2), 318– 356,  DOI: 10.1016/j.jinf.2020.04.017
      [Crossref], [PubMed], [CAS], Google Scholar
      6
      Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact
      Cantini, Fabrizio; Niccoli, Laura; Matarrese, Daniela; Nicastri, Emanuele; Stobbione, Paolo; Goletti, Delia
      Journal of Infection (2020), 81 (2), 318-356CODEN: JINFD2; ISSN:1532-2742. (Elsevier B.V.)
      Preliminary results on 12 patients with moderate COVID-19 pneumonia confirmed the safety of baricitinib therapy in a clin. context. In the baricitinib-treated group, all clin. characteristics and respiratory function parameters improved both at wk 1 and 2 compared to baseline. C-reactive protein values significantly decreased in the same timeframes. No infections, cardiovascular, and hematol. adverse events occurred after a 2 wk treatment.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVKkt7zO&md5=d47bb194919c10f50d24312f137ec88d
    7. 7
      Carfì, A.; Bernabei, R.; Landi, F.; Group, f. t. G. A. C.-P.-A. C. S. Persistent Symptoms in Patients After Acute COVID-19. JAMA 2020, 324 (6), 603– 605,  DOI: 10.1001/jama.2020.12603
      [Crossref], [PubMed], [CAS], Google Scholar
      7
      Persistent symptoms in patients after acute COVID-19
      Carfi, Angelo; Bernabei, Roberto; Landi, Francesco
      JAMA, the Journal of the American Medical Association (2020), 324 (6), 603-605CODEN: JAMAAP; ISSN:1538-3598. (American Medical Association)
      We assessed persistent symptoms in patients who were discharged from the hospital after recovery from COVID-19. Patients were assessed a mean of 60.3 days after onset of the 1st COVID-19 symptom. At the time of evaluation, only 18 (12.6%) were completely free of any COVID-19-related symptoms, while 32% had 1 or 2 symptoms and 55% had ≥3. None of the participants had fever or any signs or symptoms of acute illness. Worsened quality of life was obsd. among 44.1% of patients. A high proportion of individuals still reported fatigue (53.1%), dyspnea (43.4%), joint pain (27.3%), and chest pain (21.7%).
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs1SlsLfF&md5=d404441ba3f4ecf90c089c39b5107335
    8. 8
      Han, C.; Duan, C.; Zhang, S.; Spiegel, B.; Shi, H.; Wang, W.; Zhang, L.; Lin, R.; Liu, J.; Ding, Z. Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes. Am. J. Gastroenterol. 2020, 115 (6), 916– 923,  DOI: 10.14309/ajg.0000000000000664
      [Crossref], [PubMed], [CAS], Google Scholar
      8
      Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes
      Han Chaoqun; Duan Caihan; Zhang Shengyan; Shi Huiying; Wang Weijun; Zhang Lei; Lin Rong; Liu Jun; Ding Zhen; Hou Xiaohua; Spiegel Brennan
      The American journal of gastroenterology (2020), 115 (6), 916-923 ISSN:.
      OBJECTIVES: Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease. In this study, we sought to describe the clinical characteristics of COVID-19 patients with digestive symptoms and mild disease severity. METHODS: We identified COVID-19 patients with mild disease and one or more digestive symptoms (diarrhea, nausea, and vomiting), with or without respiratory symptoms, and compared them with a group presenting solely with respiratory symptoms. We followed up patients clinically until they tested negative for COVID-19 on at least 2 sequential respiratory tract specimens collected ≥24 hours apart. We then compared the clinical features between those with digestive symptoms and those with respiratory symptoms. RESULTS: There were 206 patients with low severity COVID-19, including 48 presenting with a digestive symptom alone, 69 with both digestive and respiratory symptoms, and 89 with respiratory symptoms alone. Between the 2 groups with digestive symptoms, 67 presented with diarrhea, of whom 19.4% experienced diarrhea as the first symptom in their illness course. The diarrhea lasted from 1 to 14 days, with an average duration of 5.4 ± 3.1 days and a frequency of 4.3 ± 2.2 bowel movements per day. Concurrent fever was found in 62.4% of patients with a digestive symptom. Patients with digestive symptoms presented for care later than those with respiratory symptoms (16.0 ± 7.7 vs 11.6 ± 5.1 days, P < 0.001). Nevertheless, patients with digestive symptoms had a longer duration between symptom onset and viral clearance (P < 0.001) and were more likely to be fecal virus positive (73.3% vs 14.3%, P = 0.033) than those with respiratory symptoms. DISCUSSION: We describe a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to have a longer delay before viral clearance, and to experience delayed diagnosis compared with patients with only respiratory symptoms.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38zmtlKmsg%253D%253D&md5=a8a5918e9e81d547aeac5e3ea3cea200
    9. 9
      Yan, C. H.; Faraji, F.; Prajapati, D. P.; Boone, C. E.; DeConde, A. S. Association of Chemosensory Dysfunction and COVID-19 in Patients Presenting with Influenza-like Symptoms. Int. Forum Allergy Rhinol. 2020, 10 (7), 806– 813,  DOI: 10.1002/alr.22579
      [Crossref], [PubMed], [CAS], Google Scholar
      9
      Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms
      Yan Carol H; Faraji Farhoud; Prajapati Divya P; DeConde Adam S; Prajapati Divya P; Boone Christine E
      International forum of allergy & rhinology (2020), 10 (7), 806-813 ISSN:.
      BACKGROUND: Rapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of coronavirus disease 2019 (COVID-19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID-19 may help facilitate screening and early isolation of cases. METHODS: A single-institution, cross-sectional study evaluating patient-reported symptoms with a focus on smell and taste was conducted using an internet-based platform on adult subjects who underwent testing for COVID-19. Logistic regression was employed to identify symptoms associated with COVID-19 positivity. RESULTS: A total of 1480 patients with influenza-like symptoms underwent COVID-19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID-19-positive patients and 203 of 1378 (15%) COVID-19-negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID-19-negative patients (p < 0.001). Smell and taste impairment were independently and strongly associated with COVID-19 positivity (anosmia: adjusted odds ratio [aOR] 10.9; 95% CI, 5.08-23.5; ageusia: aOR 10.2; 95% CI, 4.74-22.1), whereas sore throat was associated with COVID-19 negativity (aOR 0.23; 95% CI, 0.11-0.50). Of patients who reported COVID-19-associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness. CONCLUSION: In ambulatory individuals with influenza-like symptoms, chemosensory dysfunction was strongly associated with COVID-19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease-related symptoms.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38zktFCguw%253D%253D&md5=ffa5e8f95c6834fa5a14ebe51a3d0c32
    10. 10
      Mehta, P.; McAuley, D. F.; Brown, M.; Sanchez, E.; Tattersall, R. S.; Manson, J. J. U. K. COVID-19: Consider Cytokine Storm Syndromes and Immunosuppression. Lancet 2020, 395 (10229), 1033– 1034,  DOI: 10.1016/S0140-6736(20)30628-0
      [Crossref], [PubMed], [CAS], Google Scholar
      10
      COVID-19: consider cytokine storm syndromes and immunosuppression
      Mehta, Puja; McAuley, Daniel F.; Brown, Michael; Sanchez, Emilie; Tattersall, Rachel S.; Manson, Jessica J.
      Lancet (2020), 395 (10229), 1033-1034CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)
      All patients with severe COVID-19 should be screened for hyper-inflammation using lab. trends (e.g. increasing ferritin, decreasing platelet counts, or erythrocyte sedimentation rate) and the HScore to identify the subgroup of patients for whom immunosuppression could improve mortality. Therapeutic options include steroids, i.v. Ig, selective cytokine blockade (e.g. anakinra or tocilizumab) and JAK kinase inhibition.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXltFCjsb8%253D&md5=bd1ede3e6234aafcecf0547a3d768bfb
    11. 11
      Song, P.; Li, W.; Xie, J.; Hou, Y.; You, C. Cytokine Storm Induced by SARS-CoV-2. Clin. Chim. Acta 2020, 509, 280– 287,  DOI: 10.1016/j.cca.2020.06.017
      [Crossref], [PubMed], [CAS], Google Scholar
      11
      Cytokine storm induced by SARS-CoV-2
      Song, Peipei; Li, Wei; Xie, Jianqin; Hou, Yanlong; You, Chongge
      Clinica Chimica Acta (2020), 509 (), 280-287CODEN: CCATAR; ISSN:0009-8981. (Elsevier B.V.)
      A review. Coronavirus disease 2019 (COVID-19), caused by the virus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread widely throughout the world. Despite the strict global outbreak management and quarantine measures that have been implemented, the incidence of COVID-19 continues to rise, resulting in more than 290,000 deaths and representing an extremely serious threat to human life and health. The clin. symptoms of the affected patients are heterogeneous, ranging from mild upper respiratory symptoms to severe pneumonitis and even acute respiratory distress syndrome (ARDS) or death. Systemic immune over activation due to SARS-CoV-2 infection causes the cytokine storm, which is esp. noteworthy in severely ill patients with COVID-19. Pieces of evidence from current studies have shown that the cytokine storm may be an important factor in disease progression, even leading to multiple organ failure and death. This review provides an overview of the knowledge on the COVID-19 epidemiol. profile, the mol. mechanisms of the SARS-CoV-2-induced cytokine storm and immune responses, the pathophysiol. changes that occur during infection, the main antiviral compds. used in treatment strategies and the potential drugs for targeting cytokines, this information is presented to provide valuable guidance for further studies and for a therapeutic redn. of this excessive immune response.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlWns7%252FE&md5=cafd0380779103347d4867c3a893db38
    12. 12
      Thanh Le, T.; Andreadakis, Z.; Kumar, A.; Gómez Román, R.; Tollefsen, S.; Saville, M.; Mayhew, S. The COVID-19 Vaccine Development Landscape. Nat. Rev. Drug Discovery 2020, 19 (5), 305– 306,  DOI: 10.1038/d41573-020-00073-5
      [Crossref], [PubMed], [CAS], Google Scholar
      12
      The COVID-19 vaccine development landscape
      Thanh Le, Tung; Andreadakis, Zacharias; Kumar, Arun; Gomez Roman, Raul; Tollefsen, Stig; Saville, Melanie; Mayhew, Stephen
      Nature Reviews Drug Discovery (2020), 19 (5), 305-306CODEN: NRDDAG; ISSN:1474-1776. (Nature Research)
      A review on the development of vaccines for SARS-CoV-2. Topics include: the type of vaccines under development; the current stage of development; and the current no. of vaccine projects worldwide.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXnslOht7g%253D&md5=4be48c76fe66c0c69d24bebf2137eac3
    13. 13
      Graham, B. S. Rapid COVID-19 Caccine Development. Science 2020, 368 (6494), 945– 946,  DOI: 10.1126/science.abb8923
      [Crossref], [PubMed], [CAS], Google Scholar
      13
      Rapid COVID-19 vaccine development
      Graham, Barney S.
      Science (Washington, DC, United States) (2020), 368 (6494), 945-946CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)
      A review. Rapid development of a vaccine to prevent coronavirus disease 2019 (COVID-19) is a global imperative, and defining the stakes and potential hurdles is crit. because regulatory and medical decisions are based on benefit:risk calcns. The ability of viruses to achieve pandemic spread is diminished by establishing higher levels of community (herd) immunity, and a key question is whether protection against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) will happen by widespread deployment of an effective vaccine or by repeated waves of infection over the next few years until ∼60 to 70% of people develop immunity. Because the human population is naive to SARS-CoV-2, the consequences of repeated epidemics will be unacceptably high mortality, severe economic disruption, and major adjustments to our way of life. Therefore, the benefit of developing an effective vaccine is very high, and even greater if it can be deployed in time to prevent repeated or continuous epidemics.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVCntbnJ&md5=83023d5d1a0d88298e647c813eaf79f4
    14. 14
      Wu, S.-C. Progress and Concept for COVID-19 Vaccine Development. Biotechnol. J. 2020, 15 (6), e2000147– e2000147,  DOI: 10.1002/biot.202000147
      [Crossref], [PubMed], [CAS], Google Scholar
      14
      Progress and Concept for COVID-19 Vaccine Development
      Wu, Suh-Chin
      Biotechnology Journal (2020), 15 (6), 2000147CODEN: BJIOAM; ISSN:1860-6768. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review discussed the current status of coronavirus disease 2019 (COVID-19) vaccine development. Most vaccine candidates are based on the spike antigen either as inactivated vaccines, subunit vaccines, viral vectored vaccines, and nucleic acid-based DNA or mRNA vaccines.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXoslyhur4%253D&md5=d378e5bf153df53ce9bd860becacc98d
    15. 15
      Ibrahim, I. M.; Abdelmalek, D. H.; Elshahat, M. E.; Elfiky, A. A. COVID-19 Spike-Host Cell Receptor GRP78 Binding Site Prediction. J. Infect. 2020, 80 (5), 554– 562,  DOI: 10.1016/j.jinf.2020.02.026
      [Crossref], [PubMed], [CAS], Google Scholar
      15
      COVID-19 spike-host cell receptor GRP78 binding site prediction
      Ibrahim, Ibrahim M.; Abdelmalek, Doaa H.; Elshahat, Mohammed E.; Elfiky, Abdo A.
      Journal of Infection (2020), 80 (5), 554-562CODEN: JINFD2; ISSN:0163-4453. (Elsevier B.V.)
      Understanding the novel coronavirus (COVID-19) mode of host cell recognition may help to fight the disease and save lives. The spike protein of coronaviruses is the main driving force for host cell recognition. In this study, the COVID-19 spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined mol. modeling docking and structural bioinformatics. The COVID-19 spike protein is modeled using its counterpart, the SARS spike. Sequence and structural alignments show that 4 regions, in addn. to its cyclic nature have sequence and physicochem. similarities to the cyclic Pep42. Protein-protein docking was performed to test the 4 regions of the spike that fit tightly in the GRP78 Substrate Binding Domain β (SBDβ). The docking pose revealed the involvement of the SBDβ of GRP78 and the receptor-binding domain of the coronavirus spike protein in recognition of the host cell receptor. We reveal that the binding is more favorable between regions III (C391-C525) and IV (C480-C488) of the spike protein model and GRP78. Region IV is the main driving force for GRP78 binding with the predicted binding affinity of -9.8 kcal/mol. These 9 residues can be used to develop therapeutics specific against COVID-19.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVant7%252FJ&md5=d39d97ea95184f8f066318f63bb8dab1
    16. 16
      Du, L.; He, Y.; Zhou, Y.; Liu, S.; Zheng, B. J.; Jiang, S. The Spike Protein of SARS-CoV--a Target for Vaccine and Therapeutic Development. Nat. Rev. Microbiol. 2009, 7 (3), 226– 236,  DOI: 10.1038/nrmicro2090
      [Crossref], [PubMed], [CAS], Google Scholar
      16
      The spike protein of SARS-CoV - a target for vaccine and therapeutic development
      Du, Lanying; He, Yuxian; Zhou, Yusen; Liu, Shuwen; Zheng, Bo-Jian; Jiang, Shibo
      Nature Reviews Microbiology (2009), 7 (3), 226-236CODEN: NRMACK; ISSN:1740-1526. (Nature Publishing Group)
      A review. Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease caused by a novel coronavirus, SARS-coronavirus (SARS-CoV). The SARS-CoV spike (S) protein is composed of two subunits; the S1 subunit contains a receptor-binding domain that engages with the host cell receptor angiotensin-converting enzyme 2 and the S2 subunit mediates fusion between the viral and host cell membranes. The S protein plays key parts in the induction of neutralizing-antibody and T-cell responses, as well as protective immunity, during infection with SARS-CoV. In this Review, we highlight recent advances in the development of vaccines and therapeutics based on the S protein.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsFeqs7Y%253D&md5=610a46a8fed820bf5d0076e7c7d03c13
    17. 17
      Huang, Y.; Yang, C.; Xu, X.-F.; Xu, W.; Liu, S.-W. Structural and Functional Properties of SARS-CoV-2 Spike Protein: Potential Antivirus Drug Development for COVID-19. Acta Pharmacol. Sin. 2020, 41 (9), 1141– 1149,  DOI: 10.1038/s41401-020-0485-4
      [Crossref], [PubMed], [CAS], Google Scholar
      17
      Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19
      Huang Yuan; Yang Chan; Xu Xin-Feng; Xu Wei; Liu Shu-Wen; Liu Shu-Wen
      Acta pharmacologica Sinica (2020), 41 (9), 1141-1149 ISSN:.
      Coronavirus disease 2019 is a newly emerging infectious disease currently spreading across the world. It is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2, while the S2 subunit mediates viral cell membrane fusion by forming a six-helical bundle via the two-heptad repeat domain. In this review, we highlight recent research advance in the structure, function and development of antivirus drugs targeting the S protein.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38fgslensQ%253D%253D&md5=01c1cb2a20944318edd171a5869d2f84
    18. 18
      He, Y.; Zhou, Y.; Liu, S.; Kou, Z.; Li, W.; Farzan, M.; Jiang, S. Receptor-Binding Domain of SARS-CoV Spike Protein Induces Highly Potent Neutralizing Antibodies: Implication for Developing Subunit Vaccine. Biochem. Biophys. Res. Commun. 2004, 324 (2), 773– 781,  DOI: 10.1016/j.bbrc.2004.09.106
      [Crossref], [PubMed], [CAS], Google Scholar
      18
      Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine
      He, Yuxian; Zhou, Yusen; Liu, Shuwen; Kou, Zhihua; Li, Wenhui; Farzan, Michael; Jiang, Shibo
      Biochemical and Biophysical Research Communications (2004), 324 (2), 773-781CODEN: BBRCA9; ISSN:0006-291X. (Elsevier)
      The spike (S) protein of severe acute respiratory syndrome (SARS) coronavirus (CoV), a type I transmembrane envelope glycoprotein, consists of S1 and S2 domains responsible for virus binding and fusion, resp. The S1 contains a receptor-binding domain (RBD) that can specifically bind to angiotensin-converting enzyme 2 (ACE2), the receptor on target cells. Here the authors show that a recombinant fusion protein (designated RBD-Fc) contg. 193-amino acid RBD (residues 318-510) and a human IgG1 Fc fragment can induce highly potent antibody responses in the immunized rabbits. The antibodies recognized RBD on S1 domain and completely inhibited SARS-CoV infection at a serum diln. of 1:10,240. Rabbit antisera effectively blocked binding of S1, which contains RBD, to ACE2. This suggests that RBD can induce highly potent neutralizing antibody responses and has potential to be developed as an effective and safe subunit vaccine for prevention of SARS.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXotlCmsbo%253D&md5=a597ed0208b11c0af631fb72be5ee755
    19. 19
      Du, L.; Zhao, G.; He, Y.; Guo, Y.; Zheng, B.-J.; Jiang, S.; Zhou, Y. Receptor-Binding Domain of SARS-CoV Spike Protein Induces Long-Term Protective Immunity in An Animal Model. Vaccine 2007, 25 (15), 2832– 2838,  DOI: 10.1016/j.vaccine.2006.10.031
      [Crossref], [PubMed], [CAS], Google Scholar
      19
      Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model
      Du, Lanying; Zhao, Guangyu; He, Yuxian; Guo, Yan; Zheng, Bo-Jian; Jiang, Shibo; Zhou, Yusen
      Vaccine (2007), 25 (15), 2832-2838CODEN: VACCDE; ISSN:0264-410X. (Elsevier Ltd.)
      Development of effective vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is still a priority in prevention of re-emergence of SARS. Our previous studies have shown that the receptor-binding domain (RBD) of SARS-CoV spike (S) protein elicits highly potent neutralizing antibody responses in the immunized animals. But it is unknown whether RBD can also induce protective immunity in an animal model, a key aspect for vaccine development. In this study, BALB/c mice were vaccinated i.m. with 10 μg of RBD-Fc (RBD fused with human IgG1 Fc) and boosted twice at 3-wk intervals and one more time at 12th month. Humoral immune responses of vaccinated mice were investigated for up to 12 mo at a 1-mo interval and the neutralizing titers of produced antibodies were reported at months 0, 3, 6 and 12 post-vaccination. Mice were challenged with the homologous strain of SARS-CoV 5 days after the last boost, and sacrificed 5 days after the challenge. Mouse lung tissues were collected for detection of viral load, virus replication and histopathol. effects. Our results showed that RBD-Fc vaccination induced high titer of S-specific antibodies with long-term and potent SARS-CoV neutralizing activity. Four of five vaccinated mice were protected from subsequent SARS-CoV challenge because no significant virus replication, and no obvious histopathol. changes were found in the lung tissues of the vaccinated mice challenged with SARS-CoV. Only one vaccinated mouse had mild alveolar damage in the lung tissues. In contrast, high copies of SARS-CoV RNA and virus replication were detected, and pathol. changes were obsd. in the lung tissues of the control mice. In conclusion, our findings suggest that RBD, which can induce protective antibodies to SARS-CoV, may be further developed as a safe and effective SARS subunit vaccine.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXjtFGqtrY%253D&md5=a3d3a1bf9eaef5a1f1bcfd4c03b5b624
    20. 20
      Baker, A. N.; Richards, S.-J.; Guy, C. S.; Congdon, T. R.; Hasan, M.; Zwetsloot, A. J.; Gallo, A.; Lewandowski, J. R.; Stansfeld, P. J.; Straube, A. The SARS-COV-2 Spike Protein Binds Sialic Acids and Enables Rapid Detection in a Lateral Flow Point of Care Diagnostic Device. ACS Cent. Sci. 2020, 6 (11), 2046– 2052,  DOI: 10.1021/acscentsci.0c00855
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      20
      The SARS-COV-2 Spike Protein Binds Sialic Acids and Enables Rapid Detection in a Lateral Flow Point of Care Diagnostic Device
      Baker, Alexander N.; Richards, Sarah-Jane; Guy, Collette S.; Congdon, Thomas R.; Hasan, Muhammad; Zwetsloot, Alexander J.; Gallo, Angelo; Lewandowski, Jozef R.; Stansfeld, Phillip J.; Straube, Anne; Walker, Marc; Chessa, Simona; Pergolizzi, Giulia; Dedola, Simone; Field, Robert A.; Gibson, Matthew I.
      ACS Central Science (2020), 6 (11), 2046-2052CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)
      There is an urgent need to understand the behavior of the novel coronavirus (SARS-COV-2), which is the causative agent of COVID-19, and to develop point-of-care diagnostics. Here, a glyconanoparticle platform is used to discover that N-acetyl neuraminic acid has affinity toward the SARS-COV-2 spike glycoprotein, demonstrating its glycan-binding function. Optimization of the particle size and coating enabled detection of the spike glycoprotein in lateral flow and showed selectivity over the SARS-COV-1 spike protein. Using a virus-like particle and a pseudotyped lentivirus model, paper-based lateral flow detection was demonstrated in under 30 min, showing the potential of this system as a low-cost detection platform. The spike-protein from SARS-COV-2 is shown to bind sialic acids, which is exploited to assemble a lateral flow diagnostic tool, using glycans rather than antibodies, as the recognition unit.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVOlsbnP&md5=30a56fcd6d32e48834aa542773a21420
    21. 21
      Casalino, L.; Gaieb, Z.; Goldsmith, J. A.; Hjorth, C. K.; Dommer, A. C.; Harbison, A. M.; Fogarty, C. A.; Barros, E. P.; Taylor, B. C.; McLellan, J. S. Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein. ACS Cent. Sci. 2020, 6 (10), 1722– 1734,  DOI: 10.1021/acscentsci.0c01056
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      21
      Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein
      Casalino, Lorenzo; Gaieb, Zied; Goldsmith, Jory A.; Hjorth, Christy K.; Dommer, Abigail C.; Harbison, Aoife M.; Fogarty, Carl A.; Barros, Emilia P.; Taylor, Bryn C.; McLellan, Jason S.; Fadda, Elisa; Amaro, Rommie E.
      ACS Central Science (2020), 6 (10), 1722-1734CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)
      The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 28,000,000 infections and 900,000 deaths worldwide to date. Antibody development efforts mainly revolve around the extensively glycosylated SARS-CoV-2 spike (S) protein, which mediates host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2). Similar to many other viral fusion proteins, the SARS-CoV-2 spike utilizes a glycan shield to thwart the host immune response. Here, we built a full-length model of the glycosylated SARS-CoV-2 S protein, both in the open and closed states, augmenting the available structural and biol. data. Multiple microsecond-long, all-atom mol. dynamics simulations were used to provide an atomistic perspective on the roles of glycans and on the protein structure and dynamics. We reveal an essential structural role of N-glycans at sites N165 and N234 in modulating the conformational dynamics of the spike's receptor binding domain (RBD), which is responsible for ACE2 recognition. This finding is corroborated by biolayer interferometry expts., which show that deletion of these glycans through N165A and N234A mutations significantly reduces binding to ACE2 as a result of the RBD conformational shift toward the "down" state. Addnl., end-to-end accessibility analyses outline a complete overview of the vulnerabilities of the glycan shield of the SARS-CoV-2 S protein, which may be exploited in the therapeutic efforts targeting this mol. machine. Overall, this work presents hitherto unseen functional and structural insights into the SARS-CoV-2 S protein and its glycan coat, providing a strategy to control the conformational plasticity of the RBD that could be harnessed for vaccine development. The glycan shield is a sugary barrier that helps the viral SARS-CoV-2 spikes to evade the immune system. Beyond shielding, two of the spike's glycans are discovered to prime the virus for infection.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVOlsb3N&md5=52d499afcd7e3caa7d9e6017ffa86e45
    22. 22
      Xiang, F.; Wang, X.; He, X.; Peng, Z.; Yang, B.; Zhang, J.; Zhou, Q.; Ye, H.; Ma, Y.; Li, H. Antibody Detection and Dynamic Characteristics in Patients With Coronavirus Disease 2019. Clin. Infect. Dis. 2020, 71 (8), 1930– 1934,  DOI: 10.1093/cid/ciaa461
      [Crossref], [PubMed], [CAS], Google Scholar
      22
      Antibody detection and dynamic characteristics in patients with coronavirus disease 2019
      Xiang, Fei; Wang, Xiaorong; He, Xinliang; Peng, Zhenghong; Yang, Bohan; Zhang, Jianchu; Zhou, Qiong; Ye, Hong; Ma, Yanling; Li, Hui; Wei, Xiaoshan; Cai, Pengcheng; Ma, Wan-Li
      Clinical Infectious Diseases (2020), 71 (8), 1930-1934CODEN: CIDIEL; ISSN:1537-6591. (Oxford University Press)
      The coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been rapidly spreading nationwide and abroad. A serol. test to identify antibody dynamics and response to SARS-CoV-2 was developed. The antibodies against SARS-CoV-2 were detected by an ELISA based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold std. for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (rRT-PCR). The serodiagnostic power of the specific IgM and IgG antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, pos. predictive value (PPV), neg. predictive value (NPV), and consistency rate. The seroconversion of specific IgM and IgG antibodies were obsd. as early as the fourth day after symptom onset. In the patients with confirmed COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, resp., and those of IgG were 83.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9%. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, resp., and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 and rely on great specificity. The antibodies against SARS-CoV-2 can be detected in the middle and later stages of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as a complementary approach to viral nucleic acid assays.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisVWhtb%252FK&md5=c48e3aa8829f11a00738baa7ba157b67
    23. 23
      Zarzar, L. D.; Sresht, V.; Sletten, E. M.; Kalow, J. A.; Blankschtein, D.; Swager, T. M. Dynamically Reconfigurable Complex Emulsions Via Tunable Interfacial Tensions. Nature 2015, 518 (7540), 520– 524,  DOI: 10.1038/nature14168
      [Crossref], [PubMed], [CAS], Google Scholar
      23
      Dynamically reconfigurable complex emulsions via tunable interfacial tensions
      Zarzar, Lauren D.; Sresht, Vishnu; Sletten, Ellen M.; Kalow, Julia A.; Blankschtein, Daniel; Swager, Timothy M.
      Nature (London, United Kingdom) (2015), 518 (7540), 520-524CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)
      Emulsification is a powerful, well-known technique for mixing and dispersing immiscible components within a continuous liq. phase. Consequently, emulsions are central components of medicine, food and performance materials. Complex emulsions, including Janus droplets (i.e., droplets with faces of differing chemistries) and multiple emulsions, are of increasing importance in pharmaceuticals and medical diagnostics, in the fabrication of microparticles and capsules for food, in chem. sepns., in cosmetics, and in dynamic optics. Because complex emulsion properties and functions are related to the droplet geometry and compn., the development of rapid, simple fabrication approaches allowing precise control over the droplets' phys. and chem. characteristics is crit. Significant advances in the fabrication of complex emulsions have been made using a no. of procedures, ranging from large-scale, less precise techniques that give compositional heterogeneity using high-shear mixers and membranes, to small-vol. but more precise microfluidic methods. However, such approaches have yet to create droplet morphologies that can be controllably altered after emulsification. Reconfigurable complex liqs. potentially have great utility as dynamically tunable materials. Here we describe an approach to the one-step fabrication of three- and four-phase complex emulsions with highly controllable and reconfigurable morphologies. The fabrication makes use of the temp.-sensitive miscibility of hydrocarbon, silicone and fluorocarbon liqs., and is applied to both the microfluidic and the scalable batch prodn. of complex droplets. We demonstrate that droplet geometries can be alternated between encapsulated and Janus configurations by varying the interfacial tensions using hydrocarbon and fluorinated surfactants including stimuli-responsive and cleavable surfactants. This yields a generalizable strategy for the fabrication of multiphase emulsions with controllably reconfigurable morphologies and the potential to create a wide range of responsive materials.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXjsVagu70%253D&md5=6a36b3ea1d3721c03dc49e3d2766b733
    24. 24
      Zhang, W.; Liu, L. Study on the Formation and Properties of Liquid Crystal Emulsion in Cosmetic. J. Cosmet., Dermatol. Sci. Appl. 2013, 3 (2), 139– 144,  DOI: 10.4236/jcdsa.2013.32022
      [Crossref], [CAS], Google Scholar
      24
      Study on the formation and properties of liquid crystal emulsion in cosmetic
      Zhang, Wanping; Liu, Lingyan
      Journal of Cosmetics, Dermatological Sciences and Applications (2013), 3 (2), 139-144CODEN: JCDSEI; ISSN:2161-4512. (Scientific Research Publishing, Inc.)
      In this paper, the formation of liq. crystal structure in prepn. of emulsion and the change of those liq. crystal structures during storage and usage were studied. Besides, the rheol. and moisturizing property of the liq. crys- tal structure emulsion was investigated as well. The results show that the liq. crystal structure at oil-water interface in the emulsion forms gradually with cooling process after homogenization. The liq. crystal structure doesn't change significantly during the storage within 12 mo. And after emulsion being stored for 18 mo, the crystal structure starts to decomp. Upon application on the skin, the liq. crystal structure of emulsion was found to transform into other form with rubbing, although the liq. crystal structure still remains. The rheol. data shows that liq. crys- tal emulsion exhibits solid-like (elastic) property during storage, which is favorable for good stability. On the other hand, liq. crystal emulsion shows typical shear-thinning property upon usage, which leads to an excellent skin sensory feeling. And the improved moisturizing properties of such emulsion may be attributed to the liq. crystal structure.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXlvFOjsbY%253D&md5=b6ba825721d4ad73b6f153cc1598e454
    25. 25
      Masmoudi, H.; Dréau, Y. L.; Piccerelle, P.; Kister, J. The Evaluation of Cosmetic and Pharmaceutical Emulsions Aging Process using Classical Techniques and A New Method: FTIR. Int. J. Pharm. 2005, 289 (1), 117– 131,  DOI: 10.1016/j.ijpharm.2004.10.020
      [Crossref], [PubMed], [CAS], Google Scholar
      25
      The evaluation of cosmetic and pharmaceutical emulsions aging process using classical techniques and a new method: FTIR
      Masmoudi, H.; Le Dreau, Y.; Piccerelle, P.; Kister, J.
      International Journal of Pharmaceutics (2005), 289 (1-2), 117-131CODEN: IJPHDE; ISSN:0378-5173. (Elsevier B.V.)
      The purpose of this paper is to show how the utilization of Fourier Transform IR (FTIR) spectroscopy can be interesting in stability studying of cosmetic or pharmaceutical "oil in water" (O/W) emulsions. In this study temp. storage tests were performed to accelerate the aging process and evaluate the stability of five emulsions. Emulsions were analyzed by FTIR and classical methods (cond., viscosity, pH, texture anal.) in order to det. a method that would enable predicting the emulsion's stability. During the aging process, modifications of chem. functions are measured by FTIR (using spectrometric indexes), such modifications included: a decrease of unsatn. index, an increase of carbonyl index and a broadening of the carbonyl band. This band was deconvoluted to evaluate the contribution of different species in the broadening phenomenon, which seems to be caused by the appearance of free fatty acids. Conductimetry seems to be the most sensitive technique to assess phys. modifications during emulsion's aging. Concerning the most unstable emulsions, a progressive increasing of cond. was obsd. several months before the emulsion destabilizes. Consequently, FTIR and conductimetry are two complementary techniques. Conductimetry is a useful technique to predict emulsion destabilization while FTIR allows the measurement of chem. modifications and helps to understand the chem. mechanisms which occur during the oxidn.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXisFKjtg%253D%253D&md5=98e1f388771525c5242292b7dd4322e2
    26. 26
      Weinberg, G.; Ripper, R.; Feinstein, D. L.; Hoffman, W. Lipid Emulsion Infusion Rescues Dogs from Bupivacaine-Induced Cardiac Toxicity. Reg. Anesth. Pain Med. 2003, 28 (3), 198– 202,  DOI: 10.1097/00115550-200305000-00005
      [Crossref], [PubMed], [CAS], Google Scholar
      26
      Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity
      Weinberg, Guy; Ripper, Richard; Feinstein, Douglas L.; Hoffman, William
      Regional Anesthesia and Pain Medicine (2003), 28 (3), 198-202CODEN: RAPMFX; ISSN:1098-7339. (W. B. Saunders Co.)
      the authors previously demonstrated in rats that i.v. infusion of a lipid emulsion increases survival in resuscitation from severe bupivacaine cardiac toxicity. The present studies were undertaken to det. if this method is similarly effective in a non-rodent model using a larger animal. Bupivacaine, 10 mg/kg, was administered i.v. over 10 s to fasted dogs under isoflurane general anesthesia. Resuscitation included 10 min of internal cardiac massage followed with either saline or 20% lipid infusion, administered as a 4-mL/kg bolus followed by continuous infusion at 0.5 mL/kg/min for 10 min. ECG, arterial blood pressure (BP), and myocardial pH (pHm) and pO2 (pmO2) were continuously measured. Survival after 10 min of unsuccessful cardiac massage was successful for all lipid-treated dogs (n = 6), but with no survivors in the saline controls (n = 6) (P <.01). Hemodynamics, PmO2, and pHm were improved during resuscitation with lipid compared with saline treatment in which dogs did not recover. the authors found that infusing a lipid emulsion during resuscitation from bupivacaine-induced cardiac toxicity substantially improved hemodynamics, pmO2, and pHm and increased survival in dogs.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXkt1yjsL8%253D&md5=d97d8e79e2f4da5333610accccf967c1
    27. 27
      Cave, G.; Harvey, M. Intravenous Lipid Emulsion as Antidote Beyond Local Anesthetic Toxicity: A Systematic Review. Acad. Emerg. Med. 2009, 16 (9), 815– 824,  DOI: 10.1111/j.1553-2712.2009.00499.x
      [Crossref], [PubMed], [CAS], Google Scholar
      27
      Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a systematic review
      Cave Grant; Harvey Martyn
      Academic emergency medicine : official journal of the Society for Academic Emergency Medicine (2009), 16 (9), 815-24 ISSN:.
      OBJECTIVES: The objective was to asses the efficacy of lipid emulsion as antidotal therapy outside the accepted setting of local anesthetic toxicity. METHODS: Literature was accessed through PubMed, OVID (1966-February 2009), and EMBASE (1947-February 2009) using the search terms "intravenous" AND ["fat emulsion" OR "lipid emulsion" OR "Intralipid"] AND ["toxicity" OR "resuscitation" OR "rescue" OR "arrest" OR "antidote"]. Additional author and conference publication searches were undertaken. Publications describing the use of lipid emulsion as antidotal treatment in animals or humans were included. RESULTS: Fourteen animal studies, one human study, and four case reports were identified. In animal models, intravenous lipid emulsion (ILE) has resulted in amelioration of toxicity associated with cyclic antidepressants, verapamil, propranolol, and thiopentone. Administration in human cases has resulted in successful resuscitation from combined bupropion/lamotrigine-induced cardiac arrest, reversal of sertraline/quetiapine-induced coma, and amelioration of verapamil- and beta blocker-induced shock. CONCLUSIONS: Management of overdose with highly lipophilic cardiotoxic medications should proceed in accord with established antidotal guidelines and early poisons center consultation. Data from animal experiments and human cases are limited, but suggestive that ILE may be helpful in potentially lethal cardiotoxicity or developed cardiac arrest attributable to such agents. Use of lipid emulsion as antidote remains a nascent field warranting further preclinical study and systematic reporting of human cases of use.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1Mjgs12gtw%253D%253D&md5=7072e687cc8d6316e29c3967d2a6acf8
    28. 28
      Lu, T.; Spruijt, E. Multiphase Complex Coacervate Droplets. J. Am. Chem. Soc. 2020, 142 (6), 2905– 2914,  DOI: 10.1021/jacs.9b11468
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      28
      Multiphase complex coacervate droplets
      Lu, Tiemei; Spruijt, Evan
      Journal of the American Chemical Society (2020), 142 (6), 2905-2914CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      Liq.-liq. phase sepn. plays an important role in cellular organization. Many subcellular condensed bodies are hierarchically organized into multiple coexisting domains or layers. However, our mol. understanding of the assembly and internal organization of these multicomponent droplets is still incomplete, and rules for the coexistence of condensed phases are lacking. Here, we show that the formation of hierarchically organized multiphase droplets with up to three coexisting layers is a generic phenomenon in mixts. of complex coacervates, which serve as models of charge-driven liq.-liq. phase sepd. systems. We present simple theor. guidelines to explain both the hierarchical arrangement and the demixing transition in multiphase droplets using the interfacial tensions and crit. salt concn. as inputs. Multiple coacervates can coexist if they differ sufficiently in macromol. d., and we show that the assocd. differences in crit. salt concn. can be used to predict multiphase droplet formation. We also show that the coexisting coacervates present distinct chem. environments that can conc. guest mols. to different extents. Our findings suggest that condensate immiscibility may be a very general feature in biol. systems, which could be exploited to design self-organized synthetic compartments to control biomol. processes.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXht1Crtbs%253D&md5=8cdc7926ce612f24ee2adafc0339394c
    29. 29
      Galus, S.; Kadzińska, J. Food Applications of Emulsion-Based Edible Films and Coatings. Trends Food Sci. Technol. 2015, 45 (2), 273– 283,  DOI: 10.1016/j.tifs.2015.07.011
      [Crossref], [CAS], Google Scholar
      29
      Food applications of emulsion-based edible films and coatings
      Galus, Sabina; Kadzinska, Justyna
      Trends in Food Science & Technology (2015), 45 (2), 273-283CODEN: TFTEEH; ISSN:0924-2244. (Elsevier Ltd.)
      A review. An increasing awareness among consumers regarding the healthy lifestyle have prompted research on novel techniques of prolonging the shelf life of food products without the necessity of using preservatives. Thanks to their ability to improve global food quality, edible films and coatings have been particularly considered in food preservation. Changing mech. and barrier properties depending on the main component in the biopolymer matrix caused an increasing interest in composite structures, which enable to explore the complementary advantages of each component as well as to minimize their disadvantages.This review discusses the potential food applications of emulsified edible films and coatings. The materials, prepn. methods, and phys. properties are also presented. Lipids are usually added to edible films and coatings to impart hydrophobicity and thereby reduce moisture loss. A very wide range of lipid components is available including natural waxes, resins, acetoglycerides, fatty acids, and petroleum-based, mineral and vegetable oils. The emulsification process of the lipid phase in the aq. phase is necessary prior to the coating application.Emulsion-based edible films and coatings find application in fresh and processed food products, fruits and vegetables, cheeses, meat, sausages and bakery products. Composite emulsion-based edible materials produced from hydrocolloids and lipids result in better functionality than films produced with one component, esp. with respect to their water barrier properties. In general, more research is needed to improve application processes of emulsion-based edible materials, esp. sensory aspects, to be appropriate for each product.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXht1Sns7%252FL&md5=58d1cf76c6c6cb9e0c02914a2dc82e93
    30. 30
      Tavernier, I.; Wijaya, W.; Van der Meeren, P.; Dewettinck, K.; Patel, A. R. Food-Grade Particles for Emulsion Stabilization. Trends Food Sci. Technol. 2016, 50, 159– 174,  DOI: 10.1016/j.tifs.2016.01.023
      [Crossref], [CAS], Google Scholar
      30
      Food-grade particles for emulsion stabilization
      Tavernier, Iris; Wijaya, Wahyu; Van der Meeren, Paul; Dewettinck, Koen; Patel, Ashok R.
      Trends in Food Science & Technology (2016), 50 (), 159-174CODEN: TFTEEH; ISSN:0924-2244. (Elsevier Ltd.)
      The use of solid, food-grade particles as emulsion stabilizers is highly promising in the field of food science and technol. Food-grade particles (e.g. fat and wax crystals, protein particles, and protein-polysaccharide complexes) can form alternatives to inorg. particles (e.g. silica, alumina or clays), which are incompatible and mostly unserviceable when considering food and nutraceutical applications. This review provides a concise insight into the concept of Pickering stabilization with the emphasis on the available food-grade particles that have been researched in this field. The innovative food applications of particle-stabilized emulsions are also discussed.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitlSgu78%253D&md5=30b5730cb594cd78850ae5f95dd74d28
    31. 31
      Lee, D.; Weitz, D. A. Double Emulsion-Templated Nanoparticle Colloidosomes with Selective Permeability. Adv. Mater. 2008, 20 (18), 3498– 3503,  DOI: 10.1002/adma.200800918
      [Crossref], [CAS], Google Scholar
      31
      Double emulsion-templated nanoparticle colloidosomes with selective permeability
      Lee, Daeyeon; Weitz, David A.
      Advanced Materials (Weinheim, Germany) (2008), 20 (18), 3498-3503CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)
      Nanoparticle colloidosomes, shown in the SEM image, are generated by using water-in-oil-in-water double emulsions as templates. Hydrophobic silica nanoparticles that are dispersed in the oil phase stabilize the double emulsions, and subsequently become the shell of the colloidosomes upon removal of the org. solvent as shown in the figure.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXht1SgtbvF&md5=4bed920b6c55ef3aa5b191311ce03abe
    32. 32
      Bouyer, E.; Mekhloufi, G.; Rosilio, V.; Grossiord, J.-L.; Agnely, F. Proteins, Polysaccharides, and Their Complexes Used as Stabilizers for Emulsions: Alternatives to Synthetic Surfactants in the Pharmaceutical Field?. Int. J. Pharm. 2012, 436 (1), 359– 378,  DOI: 10.1016/j.ijpharm.2012.06.052
      [Crossref], [PubMed], [CAS], Google Scholar
      32
      Proteins, polysaccharides, and their complexes used as stabilizers for emulsions: Alternatives to synthetic surfactants in the pharmaceutical field?
      Bouyer, Eleonore; Mekhloufi, Ghozlene; Rosilio, Veronique; Grossiord, Jean-Louis; Agnely, Florence
      International Journal of Pharmaceutics (Amsterdam, Netherlands) (2012), 436 (1-2), 359-378CODEN: IJPHDE; ISSN:0378-5173. (Elsevier B.V.)
      A review. Emulsions are widely used in pharmaceutics for the encapsulation, solubilization, entrapment, and controlled delivery of active ingredients. In order to answer the increasing demand for clean label excipients, natural polymers can replace the potentially irritative synthetic surfactants used in emulsion formulation. Indeed, biopolymers are currently used in the food industry to stabilize emulsions, and they appear as promising candidates in the pharmaceutical field too. All proteins and some polysaccharides are able to adsorb at a globule surface, thus decreasing the interfacial tension and enhancing the interfacial elasticity. However, most polysaccharides stabilize emulsions simply by increasing the viscosity of the continuous phase. Proteins and polysaccharides may also be assocd. either through covalent bonding or electrostatic interactions. The combination of the properties of these biopolymers under appropriate conditions leads to increased emulsion stability. Alternative layers of oppositely charged biopolymers can also be formed around the globules to obtain multi-layered "membranes". These layers can provide electrostatic and steric stabilization thus improving thermal stability and resistance to external treatment. The novel biopolymer-stabilized emulsions have a great potential in the pharmaceutical field for encapsulation, controlled digestion, and targeted release although several challenging issues such as storage and bacteriol. concerns still need to be addressed.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht12jsbzI&md5=8c296ebb85fc2d35399d0f1ac7b1dc9c
    33. 33
      Sadurní, N.; Solans, C.; Azemar, N.; García-Celma, M. J. Studies on the Formation of O/W Nano-Emulsions, by Low-Energy Emulsification Methods, Suitable for Pharmaceutical Applications. Eur. J. Pharm. Sci. 2005, 26 (5), 438– 445,  DOI: 10.1016/j.ejps.2005.08.001
      [Crossref], [PubMed], [CAS], Google Scholar
      33
      Studies on the formation of O/W nano-emulsions, by low-energy emulsification methods, suitable for pharmaceutical applications
      Sadurni, Nuria; Solans, Conxita; Azemar, Nuria; Garcia-Celma, Maria Jose
      European Journal of Pharmaceutical Sciences (2005), 26 (5), 438-445CODEN: EPSCED; ISSN:0928-0987. (Elsevier B.V.)
      The formation of O/W nano-emulsions suitable for pharmaceutical application and the solubilization of a practically non-water-sol. drug, lidocaine, were studied in water/non-ionic surfactant/oil systems. Nano-emulsions were prepd. by low-energy emulsification methods, changing the compn. at const. temp. Kinetic stability was assessed by measuring droplet diam. as a function of time. Lidocaine solubilization was studied in nano-emulsions with high water content. In the water/Cremophor EL/Miglyol 812 system the lowest droplet sizes, from 14 to 39 nm at 10/90 and 40/60 oil/surfactant ratios, resp., and 90% of water content, were obtained with an emulsification method consisting of stepwise addn. of water to oil/surfactant mixts. at 70 °C. Nano-emulsions of this system showed high kinetic stability. Droplet diams. did not exceed 67 nm after a period of at least 7 mo. The max. lidocaine concn. solubilized in nano-emulsions of the water/Cremophor EL/Miglyol 812 system with 90 and 95% of water content was 3.5 and 2.1%, resp. These values are within the therapeutic range of lidocaine.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtFKns7rJ&md5=83ca304ada6773bbd988dccc958ea2ff
    34. 34
      Li, J.; Savagatrup, S.; Nelson, Z.; Yoshinaga, K.; Swager, T. M. Fluorescent Janus Emulsions for Biosensing of Listeria Monocytogenes. Proc. Natl. Acad. Sci. U. S. A. 2020, 117 (22), 11923– 11930,  DOI: 10.1073/pnas.2002623117
      [Crossref], [PubMed], [CAS], Google Scholar
      34
      Fluorescent Janus emulsions for biosensing of Listeria monocytogenes
      Li, Jie; Savagatrup, Suchol; Nelson, Zachary; Yoshinaga, Kosuke; Swager, Timothy M.
      Proceedings of the National Academy of Sciences of the United States of America (2020), 117 (22), 11923-11930CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
      Here we report a sensing method for Listeria monocytogenes based on the agglutination of all-liq. Janus emulsions. This two-dye assay enables the rapid detection of trace Listeria in less than 2 h via an emissive signal produced in response to Listeria binding. The biorecognition interface between the Janus emulsions is assembled by attaching antibodies to a functional surfactant polymer with a tetrazine/transcyclooctene click reaction. The strong binding between Listeria and the Listeria antibody located at the hydrocarbon surface of the emulsions results in the tilting of the Janus structure from its equil. position to produce emission that would ordinarily be obscured by a blocking dye. This method provides rapid and inexpensive Listeria detection with high sensitivity (<100 CFU/mL in 2 h) that can be paired with many antibody or related recognition elements to create a new class of biosensors.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlSlsbvO&md5=f8648a76e23585f89f234acf99ee7166
    35. 35
      Zentner, C. A.; Anson, F.; Thayumanavan, S.; Swager, T. M. Dynamic Imine Chemistry at Complex Double Emulsion Interfaces. J. Am. Chem. Soc. 2019, 141 (45), 18048– 18055,  DOI: 10.1021/jacs.9b06852
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      35
      Dynamic Imine Chemistry at Complex Double Emulsion Interfaces
      Zentner, Cassandra A.; Anson, Francesca; Thayumanavan, S.; Swager, Timothy M.
      Journal of the American Chemical Society (2019), 141 (45), 18048-18055CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      Interfacial chem. provides an opportunity to control dynamic materials. By harnessing the dynamic covalent nature of imine bonds, emulsions are generated in situ, predictably manipulated, and ultimately destroyed along liq.-liq. and emulsion-solid interfaces through simple perturbation of the imine equil. We report the rapid prodn. of surfactants and double emulsions through spontaneous in situ imine formation at the liq.-liq. interface of oil/water. Complex double emulsions with imine surfactants are stable to neutral and basic conditions and display dynamic behavior with acid-catalyzed hydrolysis and imine exchange. We demonstrate the potential of in situ imine surfactant formation to generate complex surfactants with biomols. (i.e., antibodies) for biosensing applications. Furthermore, imine formation at the emulsion-solid interface offers a triggered payload release mechanism. Our results illustrate how simple, dynamic interfacial imine formation can translate changes in bonding to macroscopic outputs.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitVKqsbvM&md5=72c669fb6d4faef199a392479fed257f
    36. 36
      Zeininger, L.; Nagelberg, S.; Harvey, K. S.; Savagatrup, S.; Herbert, M. B.; Yoshinaga, K.; Capobianco, J. A.; Kolle, M.; Swager, T. M. Rapid Detection of Salmonella enterica via Directional Emission from Carbohydrate-Functionalized Dynamic Double Emulsions. ACS Cent. Sci. 2019, 5 (5), 789– 795,  DOI: 10.1021/acscentsci.9b00059
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      36
      Rapid Detection of Salmonella enterica via Directional Emission from Carbohydrate-Functionalized Dynamic Double Emulsions
      Zeininger, Lukas; Nagelberg, Sara; Harvey, Kent S.; Savagatrup, Suchol; Herbert, Myles B.; Yoshinaga, Kosuke; Capobianco, Joseph A.; Kolle, Mathias; Swager, Timothy M.
      ACS Central Science (2019), 5 (5), 789-795CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)
      Reliable early-stage detection of foodborne pathogens is a global public health challenge that requires new and improved sensing strategies. Here, we demonstrate that dynamically reconfigurable fluorescent double emulsions can function as highly responsive optical sensors for the rapid detection of carbohydrates fructose, glucose, mannose, and mannan, which are involved in many biol. and pathogenic phenomena. The proposed detection strategy relies on reversible reactions between boronic acid surfactants and carbohydrates at the hydrocarbon/water interface leading to a dynamic reconfiguration of the droplet morphol., which alters the angular distribution of the droplet's fluorescent light emission. We exploit this unique chem.-morphol.-optical coupling to detect Salmonella enterica, a type of bacteria with a well-known binding affinity for mannose. We further demonstrate an oriented immobilization of antibodies at the droplet interface to permit higher selectivity. Our demonstrations yield a new, inexpensive, robust, and generalizable sensing strategy that can help to facilitate the early detection of foodborne pathogens.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXnvFCgs74%253D&md5=e62cfeb041c416f28ded00bff23beb13
    37. 37
      Zhang, Q.; Savagatrup, S.; Kaplonek, P.; Seeberger, P. H.; Swager, T. M. Janus Emulsions for the Detection of Bacteria. ACS Cent. Sci. 2017, 3 (4), 309– 313,  DOI: 10.1021/acscentsci.7b00021
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      37
      Janus Emulsions for the Detection of Bacteria
      Zhang, Qifan; Savagatrup, Suchol; Kaplonek, Paulina; Seeberger, Peter H.; Swager, Timothy M.
      ACS Central Science (2017), 3 (4), 309-313CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)
      Janus emulsion assays that rely on carbohydrate-lectin binding for the detection of Escherichia coli bacteria are described. Surfactants contg. mannose are self-assembled at the surface of Janus droplets to produce particles with lectin binding sites. Janus droplets orient in a vertical direction as a result of the difference in densities between the hydrocarbon and fluorocarbon solvents. Binding of lectin to mannose(s) causes agglutination and a tilted geometry. The distinct optical difference between naturally aligned and agglutinated Janus droplets produces signals that can be detected quant. The Janus emulsion assay sensitively and selectively binds to E. coli at 104 cfu/mL and can be easily prepd. with long-time stability. It provides the basis for the development of inexpensive portable devices for fast, on-site pathogen detection.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXks1OhsLg%253D&md5=a2f0a9d8e087ee399313d1b9a13a43b8
    38. 38
      Zhang, Q.; Zeininger, L.; Sung, K.-J.; Miller, E. A.; Yoshinaga, K.; Sikes, H. D.; Swager, T. M. Emulsion Agglutination Assay for the Detection of Protein–Protein Interactions: An Optical Sensor for Zika Virus. ACS Sens. 2019, 4 (1), 180– 184,  DOI: 10.1021/acssensors.8b01202
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      38
      Emulsion Agglutination Assay for the Detection of Protein-Protein Interactions: An Optical Sensor for Zika Virus
      Zhang, Qifan; Zeininger, Lukas; Sung, Ki-Joo; Miller, Eric A.; Yoshinaga, Kosuke; Sikes, Hadley D.; Swager, Timothy M.
      ACS Sensors (2019), 4 (1), 180-184CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)
      A new class of Janus emulsion agglutination assay is reported for the detection of interfacial protein-protein interactions. Janus emulsion droplets are functionalized with a thermally stable, antigen binding protein rcSso7d variant (rcSso7d-ZNS1) for the detection of Zika NS1 protein. The emulsion droplets contg. fluorescent dyes in their hydrocarbon and fluorocarbon phases intensify the intrinsic optical signal with the emission intensity ratio, which can be detected by a simple optical fiber. This assay provides an opportunity for the in-field detection of Zika virus and other pathogens with a stable, inexpensive, and convenient device.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXkvFaktw%253D%253D&md5=5fd06764372cdf3e3c526b8a32bfd586
    39. 39
      Zarzar, L. D.; Kalow, J. A.; He, X.; Walish, J. J.; Swager, T. M. Optical Visualization and Quantification of Enzyme Activity Using Dynamic Droplet Lenses. Proc. Natl. Acad. Sci. U. S. A. 2017, 114 (15), 3821– 3825,  DOI: 10.1073/pnas.1618807114
      [Crossref], [PubMed], [CAS], Google Scholar
      39
      Optical visualization and quantification of enzyme activity using dynamic droplet lenses
      Zarzar, Lauren D.; Kalow, Julia A.; He, Xinping; Walish, Joseph J.; Swager, Timothy M.
      Proceedings of the National Academy of Sciences of the United States of America (2017), 114 (15), 3821-3825CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
      In this paper, we describe an approach to measuring enzyme activity based on the reconfiguration of complex emulsions. Changes in the morphol. of these complex emulsions, driven by enzyme-responsive surfactants, modulate the transmission of light through a sample. Through this method we demonstrate how simple photodetector measurements may be used to monitor enzyme kinetics. This approach is validated by quant. measurements of enzyme activity for three different classes of enzymes (amylase, lipase, and sulfatase), relying on two distinct mechanisms for coupling droplet morphol. to enzyme activity (host-guest interactions with uncaging and mol. cleavage).
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXkvF2itLs%253D&md5=506744cf1dbee9a57eb93780bc58eb53
    40. 40
      Nagelberg, S.; Zarzar, L. D.; Nicolas, N.; Subramanian, K.; Kalow, J. A.; Sresht, V.; Blankschtein, D.; Barbastathis, G.; Kreysing, M.; Swager, T. M. Reconfigurable and Responsive Droplet-Based Compound Micro-Lenses. Nat. Commun. 2017, 8 (1), 14673,  DOI: 10.1038/ncomms14673
      [Crossref], [PubMed], [CAS], Google Scholar
      40
      Reconfigurable and responsive droplet-based compound micro-lenses
      Nagelberg Sara; Nicolas Natalie; Barbastathis George; Kolle Mathias; Zarzar Lauren D; Kalow Julia A; Swager Timothy M; Zarzar Lauren D; Subramanian Kaushikaram; Kreysing Moritz; Kalow Julia A; Sresht Vishnu; Blankschtein Daniel
      Nature communications (2017), 8 (), 14673 ISSN:.
      Micro-scale optical components play a crucial role in imaging and display technology, biosensing, beam shaping, optical switching, wavefront-analysis, and device miniaturization. Herein, we demonstrate liquid compound micro-lenses with dynamically tunable focal lengths. We employ bi-phase emulsion droplets fabricated from immiscible hydrocarbon and fluorocarbon liquids to form responsive micro-lenses that can be reconfigured to focus or scatter light, form real or virtual images, and display variable focal lengths. Experimental demonstrations of dynamic refractive control are complemented by theoretical analysis and wave-optical modelling. Additionally, we provide evidence of the micro-lenses' functionality for two potential applications-integral micro-scale imaging devices and light field display technology-thereby demonstrating both the fundamental characteristics and the promising opportunities for fluid-based dynamic refractive micro-scale compound lenses.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1czjsFSlug%253D%253D&md5=d719553a97e3326fd82b7a33f8f70a78
    41. 41
      van Oss, C. J.; Good, R. J.; Chaudhury, M. K. Nature of the Antigen-Antibody Interaction: Primary and Secondary Bonds: Optimal Conditions for Association and Dissociation. J. Chromatogr., Biomed. Appl. 1986, 376, 111– 119,  DOI: 10.1016/S0378-4347(00)80828-2
      [Crossref], [CAS], Google Scholar
      41
      Nature of the antigen-antibody interaction. Primary and secondary bonds: optimal conditions for association and dissociation
      Van Oss, C. J.; Good, R. J.; Chaudhury, M. K.
      Journal of Chromatography, Biomedical Applications (1986), 376 (), 111-19CODEN: JCBADL; ISSN:0378-4347.
      A review with 22 refs. discussing antigen-antibody bonds including (i) coulombic bonds, (ii) Ca2+ bridges, (iii) H-bonds, (iv) Lifshitz-van der Waals bonds, and (v) hydrophobic interactions.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL28Xkt1amur0%253D&md5=3f67e5e4e7fc2cd6fd5d7967fa0c827c
    42. 42
      Taylor, M. T.; Blackman, M. L.; Dmitrenko, O.; Fox, J. M. Design and Synthesis of Highly Reactive Dienophiles for the Tetrazine–trans-Cyclooctene Ligation. J. Am. Chem. Soc. 2011, 133 (25), 9646– 9649,  DOI: 10.1021/ja201844c
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      42
      Design and Synthesis of Highly Reactive Dienophiles for the Tetrazine-trans-Cyclooctene Ligation
      Taylor, Michael T.; Blackman, Melissa L.; Dmitrenko, Olga; Fox, Joseph M.
      Journal of the American Chemical Society (2011), 133 (25), 9646-9649CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      Computation was used to design a trans-cyclooctene deriv. that displays enhanced reactivity in the tetrazine-trans-cycloctene ligation. The optimized deriv. is an (E)-bicyclo[6.1.0]non-4-ene with a cis-ring fusion, in which the eight-membered ring is forced to adopt a highly strained half-chair' conformation. Toward 3,6-dipyridyl-s-tetrazine in MeOH at 25 °C, the strained deriv. is 19 and 27 times more reactive than the parent trans-cyclooctene and 4E-cyclooct-4-enol, resp. Toward 3,6-diphenyl-s-tetrazine in MeOH at 25°C, the strained deriv. is 160 times more reactive than the parent trans-cyclooctene.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXntVenu7Y%253D&md5=3eb79dbda8c538c9a37f77e2a83b0ac5
    43. 43
      Stephanopoulos, N.; Francis, M. B. Choosing An Effective Protein Bioconjugation Strategy. Nat. Chem. Biol. 2011, 7 (12), 876– 884,  DOI: 10.1038/nchembio.720
      [Crossref], [PubMed], [CAS], Google Scholar
      43
      Choosing an effective protein bioconjugation strategy
      Stephanopoulos, Nicholas; Francis, Matthew B.
      Nature Chemical Biology (2011), 7 (12), 876-884CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)
      A review. The collection of chem. techniques that can be used to attach synthetic groups to proteins has expanded substantially in recent years. Each of these approaches allows new protein targets to be addressed, leading to advances in biol. understanding, new protein-drug conjugates, targeted medical imaging agents and hybrid materials with complex functions. The protein modification reactions in current use vary widely in their inherent site selectivity, overall yields and functional group compatibility. Some are more amenable to large-scale bioconjugate prodn., and a no. of techniques can be used to label a single protein in a complex biol. mixt. This review examines the way in which exptl. circumstances influence one's selection of an appropriate protein modification strategy. It also provides a simple decision tree that can narrow down the possibilities in many instances. The review concludes with example studies that examine how this decision process has been applied in different contexts.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVOisbbP&md5=f635776ca8c147f5e2e1227f8eec29d8
    44. 44
      Czuban, M.; Srinivasan, S.; Yee, N. A.; Agustin, E.; Koliszak, A.; Miller, E.; Khan, I.; Quinones, I.; Noory, H.; Motola, C. Bio-Orthogonal Chemistry and Reloadable Biomaterial Enable Local Activation of Antibiotic Prodrugs and Enhance Treatments against Staphylococcus aureus Infections. ACS Cent. Sci. 2018, 4 (12), 1624– 1632,  DOI: 10.1021/acscentsci.8b00344
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      44
      Bio-Orthogonal Chemistry and Reloadable Biomaterial Enable Local Activation of Antibiotic Prodrugs and Enhance Treatments against Staphylococcus aureus Infections
      Czuban, Magdalena; Srinivasan, Sangeetha; Yee, Nathan A.; Agustin, Edgar; Koliszak, Anna; Miller, Ethan; Khan, Irfan; Quinones, Ilenis; Noory, Hasina; Motola, Christopher; Volkmer, Rudolf; Di Luca, Mariagrazia; Trampuz, Andrej; Royzen, Maksim; Mejia Oneto, Jose M.
      ACS Central Science (2018), 4 (12), 1624-1632CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)
      Systemic administration of antibiotics can cause severe side-effects such as liver and kidney toxicity, destruction of healthy gut bacteria, as well as multidrug resistance. Here, we present a bio-orthogonal chem.-based strategy toward local prodrug concn. and activation. The strategy is based on the inverse electron-demand Diels-Alder chem. between trans-cyclooctene and tetrazine and involves a biomaterial that can conc. and activate multiple doses of systemic antibiotic therapy prodrugs at a local site. We demonstrate that a biomaterial, consisting of alginate hydrogel modified with tetrazine, is efficient at activating multiple doses of prodrugs of vancomycin and daptomycin in vitro as well as in vivo. These results support a drug delivery process that is independent of endogenous environmental markers. This approach is expected to improve therapeutic efficacy with decreased side-effects of antibiotics against bacterial infections. The platform has a wide scope of possible applications such as wound healing, and cancer and immunotherapy.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXisVynsrbE&md5=cdbcf2a406c85c4e195e1c763bd33718
    45. 45
      Yoshinaga, K.; Swager, T. M. Fluorofluorescent Perylene Bisimides. Synlett 2018, 29 (19), 2509– 2514,  DOI: 10.1055/s-0037-1610224
      [Crossref], [CAS], Google Scholar
      45
      Fluorofluorescent Perylene Bisimides
      Yoshinaga, Kosuke; Swager, Timothy M.
      Synlett (2018), 29 (19), 2509-2514CODEN: SYNLES; ISSN:0936-5214. (Georg Thieme Verlag)
      Perfluorinated liqs. can exhibit immiscibility with org. solvents and water, and provide orthogonal opportunities in chem. Examples of emissive dyes that display only fluorous phase soly. are limited, despite the many potential applications. Perylene bisimides are among the most versatile dyes and are known for their outstanding stability and high quantum yields. Herein, we report the synthesis of two new "fluorofluorescent" perylene bisimide dyes, designed to be sol. in the fluorous phases. These two dyes possess unique photophys. properties, including dramatic increases in fluorescence quantum yields when treated with Bronsted acids as well as aggregation in the fluorous phase.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVWqtb3N&md5=f5e06c5dbb8d3e8d0e7a59b168a21c71
    46. 46
      Ibarrondo, F. J.; Fulcher, J. A.; Goodman-Meza, D.; Elliott, J.; Hofmann, C.; Hausner, M. A.; Ferbas, K. G.; Tobin, N. H.; Aldrovandi, G. M.; Yang, O. O. Rapid Decay of Anti-SARS-CoV-2 Antibodies in Persons with Mild Covid-19. N. Engl. J. Med. 2020, 383 (11), 1085– 1087,  DOI: 10.1056/NEJMc2025179
      [Crossref], [PubMed], [CAS], Google Scholar
      46
      Rapid Decay of Anti-SARS-CoV-2 Antibodies in Persons with Mild Covid-19
      Ibarrondo F Javier; Fulcher Jennifer A; Goodman-Meza David; Elliott Julie; Hofmann Christian; Hausner Mary A; Ferbas Kathie G; Tobin Nicole H; Aldrovandi Grace M; Yang Otto O
      The New England journal of medicine (2020), 383 (11), 1085-1087 ISSN:.
      There is no expanded citation for this reference.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38jms1OitA%253D%253D&md5=f6ec1343ea3984738792517b9b38ac90
    47. 47
      Dutta, N. K.; Mazumdar, K.; Gordy, J. T. The Nucleocapsid Protein of SARS-CoV-2: A Target for Vaccine Development. J. Virol. 2020, 94 (13), e00647– 00620,  DOI: 10.1128/JVI.00647-20
      [Crossref], [PubMed], [CAS], Google Scholar
      47
      The nucleocapsid protein of SARS-CoV-2: a target for vaccine development
      Dutta, Noton K.; Mazumdar, Kaushiki; Gordy, James T.
      Journal of Virology (2020), 94 (13), e00647-20CODEN: JOVIAM; ISSN:1098-5514. (American Society for Microbiology)
      A review. During the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there has been an un-precedented level of global collaboration that has led to a rapid characterization of SARS-CoV-2. New reports have addnl. shown that the crystal structure of the SARS-CoV-2 nucleocapsid protein is similar to those of previously described coronavirus N proteins, but their surface electrostatic potential characteristics are distinct. In this issue, Cong et al. (17) used a mouse hepatitis virus (MHV)model to show that the viral nucleocapsid (N) protein contributes to forming helical ribonucleoproteins during the packaging of the RNA genome, regulating viral RNA syn-thesis during replication and transcription and modulating metab. in infected subjects. This study complements others that have shown N to have multiple functions (25). It is becoming more evident just how crit. this protein is for multiple steps of the viral lifecycle. These reports offer important and timely insights relevant to the SARS-CoV-2 N protein, a vaccine target that has some distinct advantages over other potential SARS-CoV-2 antigen.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVKhu73I&md5=c237f78bec48e79eea76c871cdea4e5e
    48. 48
      Czajkowsky, D. M.; Shao, Z. The Human IgM Pentamer is A Mushroom-Shaped Molecule with A Flexural Bias. Proc. Natl. Acad. Sci. U. S. A. 2009, 106 (35), 14960– 14965,  DOI: 10.1073/pnas.0903805106
      [Crossref], [PubMed], [CAS], Google Scholar
      48
      The human IgM pentamer is a mushroom-shaped molecule with a flexural bias
      Czajkowsky, Daniel M.; Shao, Zhifeng
      Proceedings of the National Academy of Sciences of the United States of America (2009), 106 (35), 14960-14965, S14960/1-S14960/4CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
      The textbook planar model of pentameric IgM, a potent activator of complement C1q, is based upon the crystallog. structure of IgG. Although widely accepted, key predictions of this model have not yet been directly confirmed, which is particularly important since IgG lacks a major Ig fold domain in its Fc region that is present in IgM. Here, the authors construct a homol.-based structural model of the IgM pentamer using the recently obtained crystallog. structure of IgE Fc, which has this addnl. Ig domain, under the constraint that all of the cysteine residues known to form disulfide bridges both within each monomer and between monomers are bonded together. In contrast to the planar model, this model predicts a non-planar, mushroom-shaped complex, with the central portion formed by the C-terminal domains protruding out of the plane formed by the Fab domains. This unexpected conformation of IgM is, however, directly confirmed by cryo-at. force microscopy of individual human IgM mols. Further anal. of this model with free energy calcns. of out-of-plane Fab domain rotations reveals a pronounced asymmetry favoring flexions toward the central protrusion. This bias, together with polyvalent attachment to cell surface antigen, would ensure that the IgM pentamer is oriented on the cell membrane with its C1q binding sites fully exposed to the soln., and thus provides a mechanistic explanation for the first steps of C1q activation by IgM.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtFGnurrN&md5=aacabfc918d4057d13302c3eb140a4d1

  • Supporting Information

    Supporting Information

    ARTICLE SECTIONS
    Jump To

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acscentsci.1c00173.

    • Materials and instruments; experimental procedures; supplementary figures and tables (PDF)


    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

PDF [ 11MB]

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect