Theaflavin 3-gallate inhibits the main protease (Mpro) of SARS-CoV-2 and reduces its count in vitro

Main protease (M pro ) of SARS-CoV-2 is crucial for its replication/infection and has been recognized as an attractive drug target. In this study, we identified theaflavin 3-gallate as an inhibitor of M pro protein of SARS-CoV-2 with IC 50 value of 18.48 ± 1.29 µM. Compared to theaflavin, theaflavin 3-gallate exhibited superior antiviral activity and at a concentration of 200 µM reduced the viral count by 75% (viral particles reduced from 10 6.7 to 10 6.1 ). Time-dependent analyses of conventional and steered MD-simulations revealed stronger interactions of theaflavin 3-gallate with the active site residues of M pro than the standard molecule GC373 and theaflavin. Taken together, our findings suggest that theaflavin 3-gallate can be developed into a potential lead molecule against SARS-CoV-2.