Bioactive Molecules of Tea as Potential Inhibitors for RNA-Dependent RNA Polymerase of SARS-CoV-2.

Vijay Kumar Bhardwaj,Rituraj Purohit,Vidya Rajendran,Rahul Singh,Jatin Sharma,Sanjay Kumar

doi:10.3389/fmed.2021.684020

Abstract

The coronavirus disease (COVID-19), a worldwide pandemic, is caused by the severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2). At this moment in time, there are no specific therapeutics available to combat COVID-19. Drug repurposing and identification of naturally available bioactive molecules to target SARS-CoV-2 are among the key strategies to tackle the notorious virus. The enzyme RNA-dependent RNA polymerase (RdRp) performs a pivotal role in replicating the virus. RdRp is a prime target for Remdesivir and other nucleotides analog-based antiviral drugs. In this study, we showed three bioactive molecules from tea (epicatechin-3,5-di-O-gallate, epigallocatechin-3,5-di-O-gallate, and epigallocatechin-3,4-di-O-gallate) that showed better interaction with critical residues present at the catalytic center and the NTP entry channel of RdRp than antiviral drugs Remdesivir and Favipiravir. Our computational approach to identify these molecules included molecular docking studies, followed by robust molecular dynamics simulations. All the three molecules are readily available in tea and could be made accessible along with other medications to treat COVID-19 patients. However, these results require validation by further in vitro and in vivo studies.

Highlights

A major threat to humanity has emerged in the form of a novel coronavirus (CoV), causing a disease that is regarded as coronavirus disease 2019 (COVID-19) [1, 2]
Many studies around the world have suggested that high intake of foods rich in bioactive molecules has beneficial impact on human health and may mitigate the possibility of various human ailments, such as diabetes, FIGURE 1 | Molecular docking interaction poses of (A) Remdesivir and (B) Favipiravir with the active site of the RNA–RNA-dependent RNA polymerase (RdRp) complex of Severe Acute Respiratory Syndrome (SARS)-CoV-2
The bioactive molecules Oolonghomobisflavan-A, TheasinensinD, and Theaflavin-3-O-gallate of tea showed better binding than the FDA-approved drugs to the active site of the main protease of SARS-CoV-2 [24]

Summary

Introduction

A major threat to humanity has emerged in the form of a novel coronavirus (CoV), causing a disease that is regarded as coronavirus disease 2019 (COVID-19) [1, 2]. This virus hails to the Coronaviridae family, which contains the enveloped positive-sense RNA virus of four major groups, alpha, beta, gamma, and delta [3, 4]. Severe Acute Respiratory Syndrome (SARS) CoV and Middle East Respiratory Syndrome (MERS) CoV from the beta group are highly pathogenic to humans and develop symptoms like common cold, fever, and respiratory problems [5, 6]. As compared to the other CoVs, SARS-CoV-2 has an uplifted human-to-human transmission rate, which gives a rationale for its extensive spread [10, 11]

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