Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 36; no. 1; pp. 497 - 503
• Main Authors: Liu, Hongbo, Ye, Fei, Sun, Qi, Liang, Hao, Li, Chunmei, Li, Siyang, Lu, Roujian, Huang, Baoying, Tan, Wenjie, Lai, Luhua
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2021; Taylor & Francis Group
• Subjects: 3C-like protease; Animals; Antiviral Agents - pharmacology; baicalein; Chlorocebus aethiops; Coronavirus 3C Proteases - antagonists & inhibitors; COVID-19; COVID-19 - drug therapy; COVID-19 - enzymology; COVID-19 - virology; Drug Discovery; Enzyme Inhibitors - pharmacology; Flavanones - pharmacology; Humans; In Vitro Techniques; Models, Molecular; Plant Extracts - pharmacology; Protease Inhibitors - pharmacology; Research Paper; SARS-CoV-2; SARS-CoV-2 - drug effects; SARS-CoV-2 - enzymology; Scutellaria baicalensis; Vero Cells; Virus Replication - drug effects; COVID-19; 3C-like protease; SARS-CoV-2; baicalein; Scutellaria baicalensis
• ISSN: 1475-6366; 1475-6374; 1475-6374
• DOI: 10.1080/14756366.2021.1873977

COVID-19 has become a global pandemic and there is an urgent call for developing drugs against the virus (SARS-CoV-2). The 3C-like protease (3CL pro ) of SARS-CoV-2 is a preferred target for broad spectrum anti-coronavirus drug discovery. We studied the anti-SARS-CoV-2 activity of S. baicalensis and its ingredients. We found that the ethanol extract of S. baicalensis and its major component, baicalein, inhibit SARS-CoV-2 3CL pro activity in vitro with IC 50 's of 8.52 µg/ml and 0.39 µM, respectively. Both of them inhibit the replication of SARS-CoV-2 in Vero cells with EC 50 's of 0.74 µg/ml and 2.9 µM, respectively. While baicalein is mainly active at the viral post-entry stage, the ethanol extract also inhibits viral entry. We further identified four baicalein analogues from other herbs that inhibit SARS-CoV-2 3CL pro activity at µM concentration. All the active compounds and the S. baicalensis extract also inhibit the SARS-CoV 3CL pro , demonstrating their potential as broad-spectrum anti-coronavirus drugs.