Inhibition of SARS-CoV 3CL protease by flavonoids

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

Flavonoids are an important kind of natural products. In particular, they belong to a type of plant secondary metabolites with a polyphenolic structure widely found in fruits and vegetables. They have miscellaneous reciprocal biochemical and antioxidant effects associated with various diseases such as cancer, Alzheimer's disease and atherosclerosis [25] [26] [27] . It is due to antioxidants, anti-inflammatory, anti-mutagens and anti-cancer-causing properties combined with the ability to control major cell enzyme functions 15 . Intriguingly, some flavonoids also have antiviral activity 17 . Specifically, apigenin, luteolin, quercetin, amentoflavone 28 , quercetin, daidzein, puerarin, epigallocatechin, epigallocatechin gallate, gallocatechin gallate 29 and kaempferol 30 were reported to inhibit the proteolytic activity of SARS-CoV 3CLpro. Therefore, the antiviral effect is presumed to be directly linked to suppress the activity of SARS-CoV 3CLpro in some cases. However, the systematic analysis using various scaffolds of flavonoids was not reported. In order to find the best scaffold to inhibit the function of SARS-CoV 3CLpro, an assay with various flavonoid derivatives classified in 10 scaffolds was built and performed. Among them, the best compounds were one flavonol, herbacetin and two flavones, rhoifolin and pectolinarin. In the current assay method including 0.01% Triton X-100, the three flavonoids showed the better inhibitory activity than the previously reported flavonoids as mentioned above [28] [29] [30] . The aggregating tendency of flavonoids frequently leads to obtain false bioassay results and can be avoided by adding 0.01% Triton X-100 24 . It is worthwhile to note that amentoflavone, the most effective flavonoid inhibiting SARS-CoV 3CLpro 28 , did not effectively function in the presence of 0.01% Triton X-100 ( Figure 5) .