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

Abstract

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.