Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review.

Ridhima Kaul,Dietrich Büsselberg,Pradipta Paul,Vivek Dhar Dwivedi,Sanjay Kumar,Ali Chaari

doi:10.3390/ijms222011069

Abstract

The ongoing COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a globally leading public health concern over the past two years. Despite the development and administration of multiple vaccines, the mutation of newer strains and challenges to universal immunity has shifted the focus to the lack of efficacious drugs for therapeutic intervention for the disease. As with SARS-CoV, MERS-CoV, and other non-respiratory viruses, flavonoids present themselves as a promising therapeutic intervention given their success in silico, in vitro, in vivo, and more recently, in clinical studies. This review focuses on data from in vitro studies analyzing the effects of flavonoids on various key SARS-CoV-2 targets and presents an analysis of the structure-activity relationships for the same. From 27 primary papers, over 69 flavonoids were investigated for their activities against various SARS-CoV-2 targets, ranging from the promising 3C-like protease (3CLpro) to the less explored nucleocapsid (N) protein; the most promising were quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid. We further review promising in silico studies featuring activities of flavonoids against SARS-CoV-2 and list ongoing clinical studies involving the therapeutic potential of flavonoid-rich extracts in combination with synthetic drugs or other polyphenols and suggest prospects for the future of flavonoids against SARS-CoV-2.

Highlights

In the last two decades, human coronaviruses caused three epidemics: Severe acute respiratory syndrome coronavirus (SARS-CoV-1) in 2003, the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and recently the SARS-CoV-2, responsible for the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, from which the world is suffering since late 2019 [1,2,3]
COVID-19 is associated with severe respiratory symptoms such as pneumonia and is commonly accompanied by fever; it is caused by CoV-2, which belongs to the Betacoronavirus genus in the family Coronaviridae of the order Nidovirales [6] (Figure 1)
SARS-CoV-2, like other coronaviruses, is enveloped with crown-like particles enclosing a positive-sense single-stranded RNA, which is characterized by a 5 cap and a 3 poly

Summary

Introduction

In the last two decades, human coronaviruses caused three epidemics: Severe acute respiratory syndrome coronavirus (SARS-CoV-1) in 2003, the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and recently the SARS-CoV-2, responsible for the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, from which the world is suffering since late 2019 [1,2,3]. COVID-19 is associated with severe respiratory symptoms such as pneumonia and is commonly accompanied by fever; it is caused by CoV-2, which belongs to the Betacoronavirus genus in the family Coronaviridae of the order Nidovirales [6] (Figure 1). Members of this order share several distinctive characteristics. The Beta-coronavirus genus has its ancestor in bat CoVs and includes other viruses such as the human coronaviruses HCoV-OC43 and HCoV-HKU1, which cause the common cold. There is still much to learn about SARS-CoV-2 to define efficient therapeutic and/or preventive strategies

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