Exploring the polymerase activity of chikungunya viral non structural protein 4 (nsP4) using molecular modeling, e-pharmacophore and docking studies

Abstract

Chikungunya viral RNA-dependent RNA polymerase (RdRp) activity is conferred by non structural protein 4 (nsp4), an important protein target towards the development of antiviral compounds. The present study deals about the development of homology model of nsP4 followed by molecular docking with known RdRp inhibitors experimented in Hepatitis C virus (HCV), HIV-1, Paramyxovirus, etc. The predicted catalytic site and two allosteric binding sites were docked with nucleosidic and non-nucleosidic inhibitors. The best top five scoring ligands were selected based upon the interaction profiles and a common pharmacophore was developed. Further, RNA template-primer complex was docked within the template tunnel of modeled nsP4 to study the mode of polymerase activity.