Figure 8.

Reshaping of the S1 and S2′ subsites. Molecular-dynamics modeling of the hypothetical interaction of new-inactive M^pro with substrates is shown. Top, putative interaction with the 11-mer pseudo-substrate peptide from PDB entry 2q6g: (a) new-inactive M^pro, (b) SARS-CoV M^pro from PDB entry 2q6g. Bottom, putative interaction with the acyl-intermediate of the M^pro C-terminal autoprocessing site: (c) new-inactive M^pro, (d) M^pro in PDB entry 7khp. As a result of the rearrangement of the oxyanion loop, a new cavity near the S2′ site, labeled ‘NEW’, is formed.