In the first molecular docking exercise, we dock the geometry-optimized cyclic peptide inhibitor to the SARS-CoV M pro structure (PDB 5B6O), which we have already used for the inhibitor design. We start by defining a receptor search region to which AutoDock Vina will dock the inhibitor. The receptor search region should thus include the active site of the SARS-CoV M pro . To facilitate identification of the active site, we highlight several residues in the active site in red (Cys 38, Cys 44, Met 49, Met 165, and His 41) and then set a grid box which engulfs all of the active site as the search region (Figure ). After the molecular docking is complete, we get five docked structures, with energy scores of -10.5, -8.0, -7.8, -7.7, and -7.6 kcal/mol. In the lowest energy structure, the inhibitor fits well in the active site of SARS-CoV M pro . The P2 (Phe), P1 (Gln), P1' (Ser), and P2' (Lys) side chains of the inhibitor occupy the S2, S1, S1', and S2' pockets, and the AEPA residue occupies the S3' pocket (Figure ). This docking result demonstrates that the cyclic peptide inhibitor has the potential to bind to SARS-CoV M pro . The region to which AutoDock Vina will perform molecular docking is defined using a grid box encompassing the active site of SARS-CoV M pro . B: After molecular docking, the lowest energy conformation of the cyclic peptide inhibitor fits in the active site of SARS-CoV M pro .