Submission Details

Design Rationale:

The design is based on crystal structure Mpro-x0749. The fragment shows favorable pi stacking to Hie41 and H-bonding to Gly143. These interactions were used for a receptor based ligand design strategy for a covalent inhibitor of Cys145. The benzothiazinone partial structure was replaced by benzoimidazole to lower cLogP and the cyclohexyl side chain was replaced with a 1H-indol-6-ol partial structure to increase metabolic stability and introduce an additional H-bond to Thr26. Covalent docking shows the same binding mode as the fragment hit crystal structure.

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