Structure-based virtual screening and docking studies for the identification of novel inhibitors against wild and drug resistance strains of HIV-1 RT

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are structurally diverse group of compounds which binds to reverse transcriptase (RT) enzyme of Human Immunodeficiency Virus (HIV). Like other anti-HIV drugs, long-term clinical effectiveness of approved NNRTIs has been hampered due to the rapid development of drug resistance. Therefore, attempts have been made to discover the NNRTIs active against both drug sensitive, as well as drug resistant strains of HIV-1 RT. In the present study, using structure-based virtual screening online database of small molecules was screened against wild strain of HIV-1 RT. Among the screened ligands, top thirty hits which exhibited lowest G score against wild HIV RT were further evaluated against two clinically drug resistance strains of HIV-1 RT. Docking study of these top thirty hits revealed that around nine ligands exhibited significant binding affinity (G score less than -10) against wild, as well as two drug resistance strains of HIV-1 RT. These nine compounds were further selected for in silico prediction of physiochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters using QikProp module of Schrodinger and online tool admetSAR.