Plant-derived natural polyphenols as potential antiviral drugs against SARS-CoV-2 via RNA‐dependent RNA polymerase (RdRp) inhibition: an in-silico analysis. Issue 16 (2nd November 2021)

• Record Type: Journal Article
• Authors: Singh, Satyam; Sk, Md Fulbabu; Sonawane, Avinash; Kar, Parimal; Sadhukhan, Sushabhan
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 39:Issue 16(2021)
• Page Start: 6249
• Page End: 6264
• Publication Date: 2021-11-02
• Subjects: SARS-CoV-2 and RNA‐dependent RNA polymerase (RdRp) -- molecular docking -- molecular dynamics -- MM-PBSA -- natural polyphenols; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2020.1796810
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: The sudden outburst of Coronavirus disease (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses a massive threat to global public health. Currently, no therapeutic drug or vaccine exists to treat COVID-19. Due to the time taking process of new drug development, drug repurposing might be the only viable solution to tackle COVID-19. RNA‐dependent RNA polymerase (RdRp) catalyzes SARS-CoV-2 RNA replication and hence, is an obvious target for antiviral drug design. Interestingly, several plant-derived polyphenols effectively inhibit the RdRp of other RNA viruses. More importantly, polyphenols have been used as dietary supplementations for a long time and played beneficial roles in immune homeostasis. We were curious to study the binding of polyphenols with SARS-CoV-2 RdRp and assess their potential to treat COVID-19. Herein, we made a library of polyphenols that have shown substantial therapeutic effects against various diseases. They were successfully docked in the catalytic pocket of RdRp. The investigation reveals that EGCG, theaflavin (TF1), theaflavin-3'- O -gallate (TF2a), theaflavin-3'-gallate (TF2b), theaflavin 3, 3'-digallate (TF3), hesperidin, quercetagetin, and myricetin strongly bind to the active site of RdRp. Further, a 150-ns molecular dynamic simulation revealed that EGCG, TF2a, TF2b, TF3 result in highly stable bound conformations with RdRp. The binding free energy components calculated by the MM-PBSA also confirm the stability of the complexes. We also performed a detailed analysis of ADME prediction, toxicity prediction, and target analysis for their druggability. Overall, our results suggest that EGCG, TF2a, TF2b, TF3 can inhibit RdRp and represent an effective therapy for COVID-19. Communicated by Ramaswamy H. Sarma