Fig. 7: Clinical direct-acting antivirals (DAAs) mimic substrate binding to the SARS-CoV-2 Mpro active site. | Nature Communications

Fig. 7: Clinical direct-acting antivirals (DAAs) mimic substrate binding to the SARS-CoV-2 Mpro active site.

From: X-ray crystallographic characterization of the SARS-CoV-2 main protease polyprotein cleavage sites essential for viral processing and maturation

Fig. 7

a PF-00835231 (gray; PDB 6XHM33) superposed with C12 product (green). Hydrogen bonds common to inhibitor and product colored green, hydrogen bonds unique to product red. b PF-00835231 (gray) superposed with C6 (form2) (blue), C10 (yellow) and C14 (magenta) products, which adopt the kinked form 2 conformation. The product P3 residue projects across the S3 and S4 pockets similar to the capping indole in PF-00835231. Hydrogen bonds common to inhibitor and product colored green. c Nirmatrelvir (gray; PDB 7RFS18) superposed with C12 acyl enzyme intermediate (cyan). Hydrogen bonds common to inhibitor and product colored green, hydrogen bonds unique to product red. d Commonly observed waters (cyan spheres) in the empty Mpro active site overlaid on the C12 product structure, showing their apparent displacement upon substrate binding. Hydrogen bonds common with product are shown in black. The Mpro water positions were assessed using PDB 6YB717 and 7JOY24.

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