Inhibition of SARS-CoV 3CL protease by flavonoids

Jo, Seri; Kim, Suwon; Shin, Dong Hae; Kim, Mi-Sun

Using the library, a number of flavonoids with a wide range of inhibitory activity were detected. Intriguingly, inhibitory activities of some flavonoids were turned out to be artificial when triton X-100 was treated. Herbacetin, rhoifolin and pectolinarin were the best inhibitory compounds against SARS-CoV 3CLpro in the flavonoid library. The binding of the flavonoids was independently demonstrated by a tryptophan-based fluorescence method. In order to predict the flavonoid scaffolds needed to interact with the catalytic site of SARS-CoV 3CLpro, an induced-fit docking study was performed and analysed. The presence of additional 8hydroxyl group of herbacetin was expected to be critical to acquire its high binding affinity around the S1 and S2 sites. The occupation of the S1 and S2 sites by carbohydrate groups of rhoifolin and pectolinarin was anticipated to be another way of getting high affinity to SARS-CoV 3CLpro in glycosylated flavonoids. This study suggests that the biochemical assay combined with the docking prediction may be useful to develop better inhibitory flavonoid derivatives from various flavonoid scaffolds.