Application of 3D-QSAR Techniques in Anti-HIV-1 Drug Design - An Overview

A.   K.   Debnath

Abstract

Despite the availability of several classes of drugs against acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus type 1(HIV-1), this deadly disease showing very little sign of containment, especially in Sub-Saharan Africa and South-East Asia. More than 20 million people died since the first diagnosis of AIDS more than twenty years ago and almost 40 million people are currently living with HIV/AIDS. Structure-based drug design effort was immensely successful in identifying several drugs that are currently available for the treatment of HIV- 1. Many applications have been reported on the use of quantitative structure-activity relationship (QSAR) studies to understand the drug-receptor interactions and help in the design of more effective analogs. Extensive application was also reported on the application of 3D-QSAR techniques, such as, Comparative Molecular Field Analysis (CoMFA), Comparative Molecular Similarity Analysis (CoMSIA), pharmacophore generation using Catalyst/HypoGen, free-energy binding analysis, GRID/GOLPE, HINT-based techniques, etc. in anti-HIV-1 drug discovery programs in academia and industry. We have attempted to put together a comprehensive overview on the 3D-QSAR applications in anti-HIV-1 drug design reported in the literature during the last decade.

Keywords: hiv, reverse transcriptase, protease, integrase, gp, cxcr, ccr, comfa, comsia