Fig. 2.
Tanshinone IIA sulfonate sodium and chloroxine were identified as the inhibitors of SARS-CoV-2 PLpro. a) Screening the clinically approved drugs by the PLpro protease-activity-based assay. Z scores indicate the significance of potential inhibitors discovered. The percentage of effect indicates the inhibition rate of a compound against the PLpro protease activity. b) The dose-dependent inhibition curve of tanshinone IIA sulfonate sodium in the PLpro protease-activity-based assay. c) Screening clinically approved drugs based on the fluorescence polarization assay. d) The dose-dependent inhibition curve of chloroxine in the competitive PLpro binding-based assay. e,f) Sensorgrams of tanshinone IIA sulfonate sodium (e) and chloroxine (f) in the BLI assay at different compound concentrations. Both compounds can bind to PLpro in the BLI assay. g,h) Melting temperatures (Tm) of PLpro in the absence or presence of tanshinone IIA sulfonate sodium (g) and chloroxine (h) in the thermal shift assay at different pHs. Both compounds can alter Tm of PLpro at various pHs, which is consistent with their specific binding with PLpro.