Baicalein and Baicalin Inhibit SARS-CoV-2 RNA-Dependent-RNA Polymerase

• Type of Material: Article
• Authors: Keivan Zandi, Emory University; Katie Musall, Emory University; Adrian Oo, Emory University; Dongdong Cao, Emory University; Bo Liang, Emory University; Pouya Hassandarvish, University of Malaya; Shuiyun Lan, Emory University; Ryan L. Slack, Emory University; Karen Kirby, Emory University; Leda Bassit, Emory University; Franck Amblard, Emory University; Baek Kim, Emory University; Sazaly AbuBakar, University of Malaya; Stefan Sarafianos, Emory University; Raymond Schinazi, Emory University
• Language: English
• Date: 2021-05-01
• Publisher: MDPI AG
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/microorganisms9050893
• Title of Journal or Parent Work: Microorganisms
• Volume: 9
• Issue: 5
• Grant/Funding Information: This research was funded in part by NIH grant RO1-AI-141327 (B.K and R.F.S), Center for AIDS grant NIH grant P30-AI-050409 (R.F.S), NIH grants U54AI150472 (S.G.S) and R01AI121315 (S.G.S.). S.G.S. also acknowledges funding from the Nahmias-Schinazi Distinguished Chair in Research.
• Keywords: coronavirus; baicalein; RdRp; flavonoid; nsp12; baicalin; SARS-CoV-2; antiviral agents; COVID-19
• Research Categories: Biology, Genetics; Biology, Virology

Abstract

Coronavirus Disease 2019 (COVID-19) is a deadly emerging infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Because SARS-CoV-2 is easily transmitted through the air and has a relatively long incubation time, COVID-19 has rapidly developed into a global pandemic. As there are no antiviral agents for the prevention and treatment of this severe pathogen except for remdesivir, development of antiviral therapies to treat infected individuals remains highly urgent. Here, we showed that baicalein and baicalin exhibited significant antiviral activity against SARS-CoV-2, the causative agent of COVID-19 through in vitro studies. Our data through cell-based and biochemical studies showed that both compounds act as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors directly and inhibit the activity of the SARS-CoV-2 RdRp, but baicalein was more potent. We also showed specific binding of baicalein to the SARS-CoV-2 RdRp, making it a potential candidate for further studies towards therapeutic development for COVID-19 as a selective non-nucleoside polymerase inhibitor.