Chemical structures and in vitro biochemical and biophysical characterization of compounds that were designed to favorably interact with the S1’(C145) and S4 subsites of SARS-CoV-2 3CL pro . IC 50 is the half-maximal inhibitory concentration of the compound against the protease determined by the enzymatic inhibition assay. K d is the dissociation constant of the compound from the C145G mutant 3CL pro measured by ITC. GSH t 1/2 is the half-life of the electrophile warhead to react with glutathione. EC 50 CP and CC 50 are the half-maximal effective concentration in the presence of the P-glycoprotein efflux inhibitor CP-100356 and the half-maximal cytotoxic concentration of the compound in Vero E6 cells, respectively. Three independent experiments were performed to determine the IC 50 , GSH t 1/2 , K d , EC 50 CP , and CC 50 values.
