Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

• Main Authors: Lucianna Helene Santos, Rafaela Salgado Ferreira, Ernesto Raúl Caffarena
• Format: Article
• Language: English
• Published: Instituto Oswaldo Cruz, Ministério da Saúde 2015-11-01
• Series: Memórias do Instituto Oswaldo Cruz.
• Subjects: HIV-1; computer-aided drug design; reverse transcriptase inhibitors; molecular modelling
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762015000700847&lng=en&tlng=en

Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.