Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review

Abstract

Currently, millions of people are living with human immunodeficiency virus type 1 (HIV-1), which causes acquired immunodeficiency syndrome. However, the spread of the HIV-1 resistance to antiviral agents is the major problem in the antiretroviral therapy and medical management of HIV-infected patients. HIV-1 reverse transcriptase (RT) is one of the key viral targets for HIV-1 inhibition. Therefore, the studies on the combatting the HIV resistance that occurs due to the structural changes in RT, are in great demand. This work aims to provide an overview of the state-of-the-art molecular docking approaches applied to the studies of the HIV-1 resistance, associated with RT structure changes. We have reviewed recent studies using molecular docking with mutant forms of RT. The work discusses the modifications of molecular docking, which have been developed to find the novel molecules active against resistance mutants of RT and/or recombinant strains of HIV-1. The perspectives of the existing algorithms of molecular docking to the studies on molecular mechanisms of resistance and selection of the correct binding poses for the reverse transcriptase inhibitors are discussed.

Keywords: HIV-1; molecular docking; resistance; reverse transcriptase.

Figure 1

The structure of HIV-1 reverse transcriptase (RT). (A) an overall representation of RT; (B) the active site of RT (binding site of nucleoside reverse transcriptase inhibitors (NRTI)); (C) the allosteric site (binding site of non-nucleoside reverse transcriptase inhibitor (NNRTI)). p66 subunit is represented in green, p51 subunit is given cyan; Mg²⁺ is in yellow; zidovidine is white; nevirapine is magenta. The structures from the Protein Data Bank [27] PDB ID 3V4I [28] and 4PUO [29] were used.