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

Satyam Singh, Avinash Sonawane, Sushabhan Sadhukhan

10.26434/chemrxiv.12312263.v1

Research curated

Abstract

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.

Source: ChemRxiv

Related molecules

Name	Synonyms	Genes
Quercetagetin
Myricitrin	Myricetin, Cannabiscetin, MYC, Myricetin, Myricetol
RNA dependent RNA polymerase	RDR, viral RNA polymerase, RdRp, nsp12	rep, ORF1a-1b, RdRp
Epigallocatechin gallate	EGCG, Epigallocatechin gallate

Related interactions

Target	Drug	Type	Result
RNA dependent RNA polymerase	Quercetagetin	Computational	positive
RNA dependent RNA polymerase	Myricitrin	Computational	positive
RNA dependent RNA polymerase	Epigallocatechin gallate	Computational	positive