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Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19

  • Bapurao Surnar
    Bapurao Surnar
    Department of Biochemistry and Molecular Biology, University of Miami, 1011 NW 15th Street, Miami, Florida 33136, United States
  • Mohammad Z. Kamran
    Mohammad Z. Kamran
    Department of Biochemistry and Molecular Biology, University of Miami, 1011 NW 15th Street, Miami, Florida 33136, United States
  • Anuj S. Shah
    Anuj S. Shah
    Department of Biochemistry and Molecular Biology, University of Miami, 1011 NW 15th Street, Miami, Florida 33136, United States
    More by Anuj S. Shah
  • , and 
  • Shanta Dhar*
    Shanta Dhar
    Department of Biochemistry and Molecular Biology,  Sylvester Comprehensive Cancer Center Leonard M. Miller School of Medicine, University of Miami, 1011 NW 15th Street, Miami, Florida 33136, United States
    *Email: [email protected]
    More by Shanta Dhar
Cite this: ACS Pharmacol. Transl. Sci. 2020, 3, 6, 1371–1380
Publication Date (Web):December 1, 2020
https://doi.org/10.1021/acsptsci.0c00179
Copyright © 2020 American Chemical Society
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Abstract

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There is urgent therapeutic need for COVID-19, a disease for which there are currently no widely effective approved treatments and the emergency use authorized drugs do not result in significant and widespread patient improvement. The food and drug administration-approved drug ivermectin has long been shown to be both antihelmintic agent and a potent inhibitor of viruses such as Yellow Fever Virus. In this study, we highlight the potential of ivermectin packaged in an orally administrable nanoparticle that could serve as a vehicle to deliver a more potent therapeutic antiviral dose and demonstrate its efficacy to decrease expression of viral spike protein and its receptor angiotensin-converting enzyme 2 (ACE2), both of which are keys to lowering disease transmission rates. We also report that the targeted nanoparticle delivered ivermectin is able to inhibit the nuclear transport activities mediated through proteins such as importin α/β1 heterodimer as a possible mechanism of action. This study sheds light on ivermectin-loaded, orally administrable, biodegradable nanoparticles to be a potential treatment option for the novel coronavirus through a multilevel inhibition. As both ACE2 targeting and the presence of spike protein are features shared among this class of virus, this platform technology has the potential to serve as a therapeutic tool not only for COVID-19 but for other coronavirus strains as well.

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The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsptsci.0c00179.

  • Description of materials and methods, cell lines, chemicals, biochemicals, tables showing completed and ongoing clinical trial for different therapeutic options of COVID-19, and additional data (PDF)

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Cited By


This article is cited by 4 publications.

  1. Tean Zaheer, Kaushik Pal, Rao Zahid Abbas, María del Pilar Rodríguez Torres. COVID-19 and Ivermectin: Potential threats associated with human use. Journal of Molecular Structure 2021, 1243 , 130808. https://doi.org/10.1016/j.molstruc.2021.130808
  2. Shadpour Mallakpour, Elham Azadi, Chaudhery Mustansar Hussain. Protection, disinfection, and immunization for healthcare during the COVID-19 pandemic: Role of natural and synthetic macromolecules. Science of The Total Environment 2021, 776 , 145989. https://doi.org/10.1016/j.scitotenv.2021.145989
  3. Anna Paula A. Carvalho, Carlos A. Conte‐Junior. Recent Advances on Nanomaterials to COVID‐19 Management: A Systematic Review on Antiviral/Virucidal Agents and Mechanisms of SARS‐CoV‐2 Inhibition/Inactivation. Global Challenges 2021, 36 , 2000115. https://doi.org/10.1002/gch2.202000115
  4. Wanru Guo, Harini Lakshminarayanan, Alex Rodriguez-Palacios, Robert A Salata, Kaijin Xu, Mohamed S Draz. Glycan Nanostructures of Human Coronaviruses. International Journal of Nanomedicine 2021, Volume 16 , 4813-4830. https://doi.org/10.2147/IJN.S302516

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