A comment on saturating conditions. S-X77 (Chart S1) does not exert any inhibitory activity in concentration 20 μM or lower (Fig. ). Strikingly, however, in excess concentration, it does bind the enzyme. The MX structure of the adduct has been solved here and it shows double occupancy (See SI). This may be caused by the well-known high flexibility of the active site cavities , which allows the distorted second binding site to eventually accommodate the ligand in saturating condition. We conclude that Mpro can bind inhibitors if added in excess, forming doubly occupied adducts, even if the ligands exhibit no inhibitory activity.