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Combinatorial Chemistry & High Throughput Screening

Author(s): Abdur Rehman, Usman Ali Ashfaq, Muhammad Rizwan Javed*, Farah Shahid, Fatima Noor and Sidra Aslam*

DOI: 10.2174/1386207324666210712091920

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The Screening of Phytochemicals Against NS5 Polymerase to Treat Zika Virus Infection: Integrated Computational Based Approach

Page: [738 - 751] Pages: 14

  • * (Excluding Mailing and Handling)

Abstract

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 considered an attractive drug target.

Methods: In this study, 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 were successfully bound inside the pocket of NS5 RdRp. Polydatin was the leading phytochemical that showed high docking score -18.71 (kcal/mol) and bonding interaction at the active-site of NS5 RdRp. They were subjected to analyze drug-like properties that further reinforced their validation and showed that they have more capability to attach with the receptor as compared to SOFOSBUVIR control drug. 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 effectiveness and its biocompatibility.

Keywords: Zika virus, NS5-RdRp, phytochemicals, drugs, biocompatibility, molecular docking

Graphical Abstract

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