Plant-Derived Natural Polyphenols as Potential Antiviral Drugs Against SARS-CoV-2 via RNA‐dependent RNA Polymerase (RdRp) Inhibition: An In-Silico Analysis

18 May 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


The sudden outburst of Coronavirus disease (COVID-19) has left the entire world to a standstill. COVID-19 is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). As per the report from the WHO, more than 4.5 million people have been infected by SARS-CoV-2 with more than 3,00,000 deaths across the globe. As of now, there is no therapeutic drug or vaccine approved for the treatment of SARS-CoV-2 infection. Hence, the outbreak of COVID-19 poses a massive threat to humans. Due to the time taking process of new drug design and development, drug repurposing might be the only viable solution to tackle COVID-19. RNA‐dependent RNA polymerase (RdRp) catalyzes SARS-CoV-2 RNA replication, i.e. the synthesis of single-stranded RNA genomes, an absolutely necessary step for the survival and growth of the virus. Thus, RdRp is an obvious target for antiviral drug design. Interestingly, several plant-derived polyphenols have been shown to inhibit enzymatic activities of RdRp of various RNA viruses including polio-virus type 1, parainfluenza virus type 3, and respiratory syncytial virus etc. More importantly, natural polyphenols have been used as a dietary supplementation for humans for a long time and played a beneficial role in immune homeostasis. Therefore, we were curious to study the binding of dietary polyphenols with RdRp of SARS-CoV-2 and assess their potential as an effective therapy for COVID-19. In this present work, we made a library of twenty potent polyphenols that have shown substantial therapeutic effects against various diseases. The polyphenols were successfully docked in the catalytic pocket of RdRp of SARS-CoV and SARS-CoV-2, and detailed studies on ADME prediction, toxicity prediction and target analysis were performed. The study reveals that EGCG, quercetagetin, and myricetin strongly bind to the active site of SARS-CoV-2 RdRp. Our studies suggest that EGCG, quercetagetin, and myricetin can inhibit RdRp and represent an effective therapy for COVID-19.


RNA‐dependent RNA polymerase (RdRp)
Docking studies
Natural polyphenols


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