HIV-۱ glycoprotein ۴۱ molecular docking analysis andtransmitted drug resistance mutations among antiretroviral therapynaïveindividuals in Iranian patients

Background and Aim : HIV gp۴۱ protein plays a critical role in membrane fusion, which helpsHIV to infect the host cells. Three inhibitors (T۲۰, VIR-۵۷۶ and C۳۴) were introduced recently totarget this protein. However, mutations in this region might reduce their efficacy. This study, asthe first report of Iran, aimed to investigate gp۴۱ mutations amongst Iranian patients to define thepossible efficiency of gp۴۱ inhibitors in the treatment of the patient.Methods : ۳۰ patients’ RNA sera was extracted and then amplified the gp۴۱ 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 fusion inhibitors and gp۴۱ 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 gp۴۱ proteins cannot reduce the fusion inhibitors efficacy. The most prevalentsubtype amongst the samples was A۱, and several post-modification positions includingglycosylation and phosphorylation sites were identified.Conclusion : Our findings showed that despite numerous mutations in enrolled samples, gp۴۱inhibitors, could still be effective in inhibiting HIV infections in Iranian patients. Additionally, thepresent study introduced a new gp۴۱ region (۳۶-۴۴ aa) which has considerable influence in theinteractions between gp۴۱ inhibitors and gp۴۱ protein. Moreover, subtyping results demonstratethat HIV-Pol gene is more specific region of subtyping among Iranian patients than gp۴۱ gene.

Keywords:

HIV , gp۴۱ , Drug resistance , Docking , Fusion inhibitors , Iran