Fig. 14.

Frequency of residues present in ligand-3CL^pro complexes (A) found in the literature and compound N3 in complex with eight most frequent amino acid residues of the pocket 1 (B) from SARS-CoV 3CL^pro (PDB ID: 2HOB). In B), covalent Cys¹⁴⁵ residue is shown as blue color, exhibiting its connectivity to Michael’s acceptor moiety. Finally, the most frequent amino acid residues from pocket 1 are demonstrated in a molecular surface overview (in orange color). In C), the Michael’s acceptor N3, a peptide-derived, which has been explored in different works, where it has been identified as a promising inhibitor of 3CL^pro from MERS-CoV (IC₅₀ = 0.28 µM),²¹⁹ SARS-CoV-2 (EC₅₀ = 16.77 µM),²⁷³ GS-WT₁₂ (K_i = 9.0 ± 0.8 µM), WT-GPH₆ (K_i = 2.3 ± 0.1 µM), and WT (K_i = 1.9 ± 0.1 µM) modified proteases.²⁸³.