The Screening of phytochemicals against NS5 Polymerase to treat Zika Virus infection: Integrated computational based approach.

Background The recent Zika virus (ZIKV) outbreak provides a spur for new, efficient, and safe anti-Zika Virus agents. RNA-dependent RNA polymerase (RdRp) is critical amongst the seven non-structural proteins for viral replication and is considered an attractive drug target. Methods In this study, a molecular docking approach was used to rationally screen the library of 5000 phytochemicals to find inhibitors against NS5 RdRp. LigX tool was used to analyze the 2D plots of receptor-ligand interactions. The top-ranked compounds were then subjected to in-silico pharmacokinetic study. Results The compounds, namely Polydatin, Dihydrogenistin, Liquiritin, Rhapontin, and Cichoriin, successfully bind inside the pocket of NS5 RdRp. Polydatin was the leading phytochemical that showed high docking score of -18.71 (kcal/mol) and bonding interaction at the active site of NS5 RdRp. They were subjected to analysis for drug-like properties that further reinforced their validation and showed that they could attach with the receptor more than SOFOSBUVIR control drugs. MD simulation of the top two complexes was performed, and the simulated complexes showed stability, and ligands were kept within the bonding pocket. Conclusion The study might facilitate the development of a natural and cost-effective drug against ZIKV. Further validation, however, is necessary to confirm its drug effectiveness and its biocompatibility.