Researching of resistance to etravirine in some HIV-1 low-level viremia strains by in-silico methods

Abstract Objectives Human immunodeficiency virus (HIV) is a significant infection that attacks immune system cells and integrates its genetic material into host cells. Left untreated, it leads to acquired immunodeficiency syndrome (AIDS). Antiretroviral therapy (ART) is used to control HIV infection. Etravirine (ETR) is an important non-nucleoside reverse transcriptase inhibitor (NNRTI) utilized in the treatment of HIV. Low-level viremia (LLW) is a serious clinical condition, and the underlying mechanisms remain incompletely understood. The aim of our study is to analyze and elucidate the resistance status of Lys104Gln, Lys102Gln, Lys101Arg-Lys104Arg, Ser191Phe, Ile94Leu-Lys104Arg, Lys104Glu-His235Leu, Ala98Ser and Val179Ile mutations using in-silico methods, which are identified as low-level viremic strains, because their resistance status to ETR is unknown. Methods Homology modeling was performed using the Swiss Model program. Molecular docking of ETR with the reverse transcriptase (RT) enzyme was conducted using the CB-Dock program developed by AutoDock Vina. Protein-ligand interaction analysis was carried out using the protein-ligand interaction profiler (PLIP). Results A98S and V179I mutations altered the physicochemical properties of the region, resulting in changes to the conformational structure of the NNRTI hydrophobic pocket compared to the wild-type and consequently decreased docking scores. Conclusions Based on the evaluation of literature data and in-silico analyses, it is believed that A98S and V179I mutations may alter the conformational structure of the hydrophobic pocket where ETR binds, potentially resulting in low-level resistance against ETR.