Fig. 3: Crystal structure of RAY1216 in complex with SARS-CoV-2 Mpro.
a, Cartoon representation of the dimeric Mpro bound to RAY1216. Protomer A is in green, protomer B is in blue and RAY1216 is shown as yellow ball-and-stick models in active sites of both Mpro protomers. Asterisks mark structural features from protomer B. b, A zoom-in view of the RAY1216-bound active site of protomer A. An electron density (2Fo-Fc) map (blue mesh, contoured at 1.3σ) is shown around the bound RAY1216 and the catalytic Cys145 side chain (also see Supplementary Fig. 10 for omit map densities). Clear electron density is observed for the thiohemiketal bond formed between the bound RAY1216 α-keto carbon and the catalytic Cys145 sulfur. c, Same view as in b showing detailed interactions between RAY1216 and the active site of Mpro. Selected side chains of interacting residues are shown; backbone carbonyl and amide are represented as red and blue dots. d, Detailed interactions between PF-07321332 and the active site of Mpro (based on PDB 7RFW (ref. 6)) are shown in the same view as in c. In c and d, molecular surfaces of selected residues involved in hydrophobic contacts with bound inhibitors are shown. Hydrogen bonds are shown in dashed lines. Extra hydrogen bonds formed by RAY1216 to Mpro or hydrogen bonds of different properties to Mpro between RAY1216 and PF-07321332 are highlighted with colours.
