The conformation adopted by both compounds in the active site of M pro can be compared with the X-ray crystal structures of related complexes. Thus, the cocrystal structure of the covalent adduct of PF-00835231 bound to SARS CoV-2 3CLpro (PDB code 6XHM) that, as commented above is like B4, shows protein-ligand distances in S1, S2 and S3 equivalent to the ones shown in Figure . These similarities are also observed when comparing the distances between the key atoms involved in the inhibition reaction, Sg C45 -C C=O , Sg C45 -Ne H41 and Ne H41 -O* OH : 1.86, 3.71 and 3.80 Å, respectively, in the crystal structure, and 2.90, 3.13 and 2.34 Å, respectively, in the B4. Regarding the B3, despite no X-ray structure is available for SARS CoV-2 M pro complexed with a structure comparable to B3, there is a cocrystal structure of the covalent adduct 2 of Hoffman and co-workers bound to SARS CoV-1 3CLpro (PDB code 6XHO). Analysis of these structure provide similar conclusions regarding the interactions between the different subsites of the active site of the related proteins, CoV-1 and CoV-2 M pro , and the corresponding compounds in the X-ray structure of SARS CoV-1 3CLpro and B3 in SARS CoV-2 M pro . Obviously, the absence of the carbonyl group at a position of P1' in 2 explains the lack of the interactions with the oxyanion hole of the S1' site. Nevertheless, the comparison of the inter-atomic distances that are related with the inhibition reaction, Sg C45 -Cb, Sg C45 -Ne H41 , and Ne H41 -Ca, also shows similar values: 1.76, 3.96 and 3.23 Å, respectively, in the crystal structure, and 3.29, 3.29 and 4.09 Å, respectively, in B3.