Phylogenetic analysis, structure modeling and docking study of HCV NS3 protease for the identification of potent inhibitors

Abstract The nonstructural protein 3 (NS3) helicase of HCV is believed to be a plausible target for the identification and designing of potent antiviral drugs. NS3 protein is involved in a positive sense single-stranded viral replication as well as it also cleaves viral poly protein into diverse mature proteins at different time spans. Structural exploration of NS3 revealed that HCV helicase could also act as translocase. In order to identify potential inhibitors for HCV-3a, the current study has been designed. Serum samples from the Pakistani HCV positive patients were collected, sequenced and after purification included in the present study. Phylogenetic analysis on the samples clustered around it in the same group with those from India. Using homology modeling technique, we determined 3D structure of NS3 gene of HCV-3a and employed further in docking studies to discover potent inhibitor against it. As a result of docking Compound 1, with IC50 value of 0.015 and −14.4 kcal/mol energy, ranked as a most pungent inhibitor among all the studied inhibitors. Compound 1 also exhibited good hydrogen bond interactions with the modeled protein. The finding of present study could be used as a lead in future to design an effective dual inhibitor against HCV-3a.