Computational Protein–Ligand Docking to EvaluateSusceptibility to HIV Gag Inhibitors in HIV-Infected Iranian Patients

Background and Aim : HIV Gag protein plays a critical role in virus assembly and maturation,which helps HIV to establish a productive infection. Twelve inhibitors were introduced recentlyto target this protein. However, mutations in this region might reduce their efficacy. This study, asthe first report of Iran, aimed to investigate Gag mutations amongst Iranian patients to define thepossible efficiency of Gag inhibitors in the treatment of the patient.Methods : ۴۰ patients’ RNA sera was extracted and then amplified the Gag region using NestedPCR. The sequences were analyzed to define mutations, physicochemical properties, postmodificationpositions, structural analysis, and subtyping via Bioinformatics tools and finally, thepossible docking interaction of Gag inhibitors and Gag proteins were examined.Results : As the first report of Iran, several mutations were found in comparison with the twoselected references that docking analysis showed such substitution in the interaction site of fusioninhibitors and Gag proteins cannot reduce the Gag inhibitors efficacy. The most prevalent subtypeamongst the samples was A۱-D, and several post-modification positions including glycosylationand phosphorylation sites were identified.Conclusion : Our findings showed that despite numerous mutations in enrolled samples, Gaginhibitors, could still be effective in inhibiting HIV infections in Iranian patients. Additionally, thepresent study introduced new several regions which have considerable influence on theinteractions between Gag inhibitors and Gag protein.

Keywords:

HIV , Gag inhibitors , Drug resistance , Gag , molecular docking