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Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors
Helene Santos, Lucianna; Salgado Ferreira, Rafaela & Raúl Caffarena, Ernesto
Abstract
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.
Keywords
HIV-1; computer-aided drug design; reverse transcriptase inhibitors; molecular modelling
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