A Multivariate Analysis of HIV-1 Protease Inhibitors and Resistance Induced by Mutation

Anna Maria Almerico,* Marco Tutone, Antonino Lauria, Patrizia Diana, Paola Barraja, Alessandra Montalbano, Girolamo Cirrincione, and Gaetano Dattolo
Dipartimento Farmacochimico, Tossicologico e Biologico, Universit degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy
J. Chem. Inf. Model., 2006, 46 (1), pp 168–179
DOI: 10.1021/ci050139z
Publication Date (Web): November 12, 2005
Copyright © 2006 American Chemical Society
*

 Corresponding author tel.:  +39 0916161606; fax +39 0916169999; e-mail:  almerico@unipa.it.

Abstract

This paper describes the use of the multivariate statistical procedure principal component analysis as a tool to explore the inhibitory activity of classes of protease inhibitors (PIs) against HIV-1 viruses (wild type and more-frequent single mutants, V82A, V82F, and I84V) and against protease enzymes. The analysis of correlations between biological activity and molecular descriptors or similarity indexes allowed a reliable classification of the 51 derivatives considered in this study. The best results were obtained in the case of the I84V mutant for which a high number of predictions was achieved. On this basis, this statistical approach is proposed as a reliable method for the prediction of the activity of PIs, for which the data against mutant strains have not been reported.

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History

  • Published In Issue January 23, 2006
  • Received April 20, 2005

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