Figure 4.

Substrate-binding cleft of M^PRO, the endogenous protease in SARS-CoV-2, with compound 13b, a peptidomimetic α-ketoamide inhibitor of the viral enzyme. Fo-Fc density is shown for the inhibitor. Atom color rendering: magenta, carbon (except in the pyridone ring, which is black), red, oxygen; blue, nitrogen, and yellow, sulfur. Light-blue symbols S1, S2, S3, S4 indicate the canonical binding pockets for moieties P1, P2, P3, P4 (red symbols) inhibitor. Red dashed lines represent H-bonds. Inset: Thiohemiketal resulting from the nucleophilic attack of the catalytic Cys residue on the α-carbon of the inhibitor in its Fo-Fc density (contoured at 3σ). From Zhang L. et al. (2020), held under Creative Commons license.