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

Abstract

<p>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>i.e.</i> 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. </p>

An in-silico study on selected organosulfur compounds as potential drugs for SARS-CoV-2 infection via binding multiple drug targets

“…From all the above studies, we projected that the organosulfur compounds are potential class of molecules to inhibit various proteins of SARS-CoV-2 and thus can be potential drugs against the menace. The other types of organic molecules which are capable to serve as drugs against the COVID-19 are plant derived polyphenols [45] , corticosteroids [46] , flavonoids [47] , peptidyl analogues [48] etc. along with other biologicals such as antibodies and therapeutic RNA [49] .…”

Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach

“…As previously mentioned, RdRp catalyzes SARS-CoV-2 RNA replication and thereby is considered an important target for antiviral drug design. Molecular docking investigation revealed that EGCG, theaflavin, theaflavin-3′- O -gallate, theaflavin-3′-gallate, theaflavin 3,3′-digallate, hesperidin, quercetagetin, and myricetin bind to the active site of RdRp ( Singh et al, 2020 ). Overall, flavonoids and indole chalcones could combat SARS-CoV-2 ( Vijayakumar et al, 2020 ).…”

“…Theaflavins, a group of polyphenols formed after the fermentation of green tea, have a very strong affinity to bind to RdRp ( Lung et al, 2020 ; Singh et al, 2020 ). Lung and co-workers reported that theaflavin had a high affinity for RdRp of SARS-CoV2, SARS-CoV, and MERS-CoV ( Lung et al, 2020 ).…”

New Insights Into Potential Benefits of Bioactive Compounds of Bee Products on COVID-19: A Review and Assessment of Recent Research

“…This compound has been consumed since a time long ago and does not possess any inherent toxicity besides exhibiting a broad range of therapeutic properties, suggesting the potential use of this natural compound as inhibitor for RdRp of SARS-CoV-2. However, additional in vitro and in vivo studies seem mandatory to validate its efficaciousness against SARS-CoV-2 ( Singh et al, 2020 ).…”