Fig. 2. X-ray crystallographic structures of SARS-CoV-2 M^pro cleavage sites C4 to C10.

a, b and d–i show product-like complexes with the C145A mutant, c shows an acyl-enzyme (AE) intermediate complex with wild-type (WT) M^pro. The complementary substrate specificity residues (P6-P1) are labeled and shown as ball-and-stick (carbons are green) bound into the M^pro substrate binding groove shown as a molecular surface (carbons are gray). The Schechter–Berger substrate specificity pockets (S1, S2, and S4 in M^pro) are labeled. Enzyme residues near the cleavage site atoms are labeled on the molecular surface. Non-carbon atoms are colored as follows: oxygen - red, nitrogen - blue, sulfur - yellow. The C5 C145A (b) and WT (c) structures were determined previously²⁴ with PDB 7JOY and 7KHP, respectively, used to make the figure.