Fig. 6: The X-ray crystal structure of SARS-CoV-2 Mpro in complex with 5h.
a SARS-CoV-2 Mpro is shown in ribbon and 5h in ball and stick representation. The two protomers of Mpro are shown in green and blue ribbons, and 5h in pink. Nitrogen, oxygen, and sulfur atoms are shown in blue, red and yellow, respectively. Each protomer consists of three domains (only one protomer is labeled for clarity) and domains I and II mostly comprise of b-sheets and loops and forming the binding pocket. b Hydrophobicity of the binding pocket is represented by the intensities of red color, hydrophobic residues such as Leu-27 and Met-165 are shown in dark red, whereas polar or charged residues such as Glu-166, Gln-189 are shown in light red. While the distal edge of 4-methoxyindole-2-carbonyl group is surrounded by Pro-168 and Ala-191 on the top, the center part of the moiety faces to Met-165, which lies in the interior part of the binding groove. c Hydrogen bond interactions between 5h (pink carbon atoms) and Mpro (green carbon atoms) are shown in black dashed lines. 5h forms 8 direct hydrogen bonds with Mpro residues, additional polar interactions are mediated by water molecules (red spheres). d A 90°-rotated view of 5h focuses on the interactions of 2-oxopyrrolidine and benzothiazole groups. While the nitrogen of 2-oxopyrrolidine forms hydrogen bonds with the carboxylate oxygen of Glu-166 and carbonyl oxygen of Phe-140, the oxygen of 2-oxopyrrolidine forms a hydrogen bond with the imidazole group of His-163. The nitrogen of the P1′ benzothiazole forms water-mediated hydrogen bonds with the backbone NH of Gly-143 and carbonyl oxygen of Thr-26. e The hydroxyl group of 5h is shown in the center, which forms a strong hydrogen bond with the backbone amide of Cys-145 (2.9 Å). Distances between atoms are shown in Å.
