8B56
Crystal structure of SARS-CoV-2 main protease (MPro) in complex with the inhibitor GD-9
Summary for 8B56
| Entry DOI | 10.2210/pdb8b56/pdb |
| Descriptor | 3C-like proteinase nsp5, (2~{S})-4-(2-chloranylethanoyl)-1-(3,4-dichlorophenyl)-~{N}-(thiophen-2-ylmethyl)piperazine-2-carboxamide, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | sars-ncov, main protease, covalent inhibitor, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus |
| Total number of polymer chains | 2 |
| Total formula weight | 68695.46 |
| Authors | Straeter, N.,Muller, C.E.,Claff, T.,Sylvester, K.,Weisse, R.,Gao, S.,Song, L.,Liu, X.,Zhan, P. (deposition date: 2022-09-21, release date: 2023-08-09, Last modification date: 2024-11-06) |
| Primary citation | Gao, S.,Song, L.,Claff, T.,Woodson, M.,Sylvester, K.,Jing, L.,Weisse, R.H.,Cheng, Y.,Strater, N.,Schakel, L.,Gutschow, M.,Ye, B.,Yang, M.,Zhang, T.,Kang, D.,Toth, K.,Tavis, J.,Tollefson, A.E.,Muller, C.E.,Zhan, P.,Liu, X. Discovery and Crystallographic Studies of Nonpeptidic Piperazine Derivatives as Covalent SARS-CoV-2 Main Protease Inhibitors. J.Med.Chem., 65:16902-16917, 2022 Cited by PubMed Abstract: The spread of SARS-CoV-2 keeps threatening human life and health, and small-molecule antivirals are in demand. The main protease (M) is an effective and highly conserved target for anti-SARS-CoV-2 drug design. Herein, we report the discovery of potent covalent non-peptide-derived M inhibitors. A series of covalent compounds with a piperazine scaffold containing different warheads were designed and synthesized. Among them, was identified as the most potent compound with a significant enzymatic inhibition of M (IC = 0.18 μM) and good antiviral potency against SARS-CoV-2 (EC = 2.64 μM), similar to that of remdesivir (EC = 2.27 μM). Additionally, presented favorable target selectivity for SARS-CoV-2 M versus human cysteine proteases. The X-ray co-crystal structure confirmed our original design concept showing that covalently binds to the active site of M. Our nonpeptidic covalent inhibitors provide a basis for the future development of more efficient COVID-19 therapeutics. PubMed: 36475694DOI: 10.1021/acs.jmedchem.2c01716 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.823 Å) |
Structure validation
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