Scutellaria baicalensisextract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like proteasein vitro

COVID-19 has become a global pandemic that threatens millions of people worldwide. There is an urgent call for developing effective drugs against the virus (SARS-CoV-2) causing this disease. The main protease of SARS-CoV-2, 3C-like protease (3CL^pro), is highly conserved across coronaviruses and is essential for the maturation process of viral polyprotein. Scutellariae radix (Huangqin in Chinese), the root ofScutellaria baicalensishas been widely used in traditional Chinese medicine to treat viral infection related symptoms. The extracts ofS. baicalensishave exhibited broad spectrum antiviral activities. We studied the anti-SARS-CoV-2 activity ofS. baicalensisand its ingredient compounds. We found that the ethanol extract ofS. baicalensisinhibits SARS-CoV-2 3CL^proactivityin vitroand the replication of SARS-CoV-2 in Vero cells with an EC₅₀of 0.74 μg/ml. Among the major components ofS. baicalensis, baicalein strongly inhibits SARS-CoV-2 3CL^proactivity with an IC₅₀of 0.39 μM. We further identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CL^proactivity at microM concentration. Our study demonstrates that the extract ofS. baicalensishas effective anti-SARS-CoV-2 activity and baicalein and analogue compounds are strong SARS-CoV-2 3CL^proinhibitors.