Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds

The 3C-like protease (3CL(pro)) of SARS-coronavirus mediates the proteolytic processing of replicase polypeptides 1a and 1ab into functional proteins, becoming an important target for the drug development. In this study, Isatis indigotica root extract, five major compounds of I. indigotica root, and seven plant-derived phenolic compounds were tested for anti-SARS-CoV 3CL(pro) effects using cell-free and cell-based cleavage assays. Cleavage assays with the 3CL(pro) demonstrated that IC(50) values were in micromolar ranges for I. indigotica root extract, indigo, sinigrin, aloe emodin and hesperetin. Sinigrin (IC(50): 217 μM) was more efficient in blocking the cleavage processing of the 3CL(pro) than indigo (IC(50): 752 μM) and beta-sitosterol (IC(50): 1210 μM) in the cell-based assay. Only two phenolic compounds aloe emodin and hesperetin dose-dependently inhibited cleavage activity of the 3CL(pro), in which the IC(50) was 366 μM for aloe emodin and 8.3 μM for hesperetin in the cell-based assay.