Inhibition of SARS-CoV 3CL protease by flavonoids

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

The glide scores of rhoifolin and pectolinarin were -9.565 and -8.054, respectively. They belong to the flavone family. Interestingly, their binding modes are different from those of the above three flavonols. Rhoifolin and pectolinarin possess a-L-rhamnopyranosyl b-D-glucopyranoside and L-mannopyranosyl b-D-glucopyranoside, respectively. The additional bulky carbohydrate groups are attached to 7-position of the chromen-4-one scaffold. As a result, the hydrogen bond formed between the 7-hydroxyl group and the backbone of Ile188 was abolished. In addition, the bulky groups require a large space to reside in. Therefore, these carbohydrate groups occupy the S1 and S2 sites and the chromen-4-one moieties locate in the S2 and S3 0 sites, unlike the above three flavonols. The better affinity of rhoifolin may be due to orchestrated binding through S1, S2 and S3' sites.