9M2V
Crystal Structure of the SARS-CoV-2 (COVID-19) main protease with inhibitor MC12
This is a non-PDB format compatible entry.
Summary for 9M2V
| Entry DOI | 10.2210/pdb9m2v/pdb |
| Descriptor | 3C-like proteinase nsp5, [2-[methyl(phenyl)amino]-1,3-thiazol-4-yl]methanol (3 entities in total) |
| Functional Keywords | covid19, mpro, main protease, viral protein, covalent bond, 3cl, sars-cov2 |
| Biological source | Severe acute respiratory syndrome coronavirus 2 |
| Total number of polymer chains | 1 |
| Total formula weight | 34520.25 |
| Authors | |
| Primary citation | Yin, W.,Kong, W.P.,Leung, S.L.,Hung, C.H.,Wong, K.Y. Structure-activity relationship studies of thiazole-based derivatives leading to the identification of novel and potent SARS-CoV-2 main protease inhibitors. Eur.J.Med.Chem., 297:117952-117952, 2025 Cited by PubMed Abstract: The COVID-19 pandemic has highlighted the need for effective antiviral agents targeting SARS-CoV-2. This study presents the development of thiazole-based inhibitors against SARS-CoV-2 Main Protease, a key enzyme for viral replication. Using Masitinib and MAC-5576 as leads, we designed 29 compounds featuring a pyridinyl ester for covalent binding to Cys145 and a thiazole core for S2 subsite interaction. Structure-activity relationship (SAR) analysis identified the pyridinyl ester as a critical pharmacophore, with the thiazole core providing superior inhibition compared to oxazole. Compound MC12 (IC = 77.7 ± 14.1 nM) demonstrated inhibitory activities comparable to Nirmatrelvir (IC = 58.4 ± 8.6 nM). Mass spectrometry and X-ray crystallography confirmed reversible covalent binding of MC compounds to SARS-CoV-2 Main Protease. These compounds also showed low cytotoxicity and dual inhibition of SARS-CoV and SARS-CoV-2 M. Thiazole-based compounds thus emerge as promising leads for developing potent and safe SARS-CoV-2 M inhibitors. PubMed: 40644922DOI: 10.1016/j.ejmech.2025.117952 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.967 Å) |
Structure validation
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