9OCK
Co-Structure of Main Protease of SARS-CoV-2 with Compound 1
This is a non-PDB format compatible entry.
Summary for 9OCK
| Entry DOI | 10.2210/pdb9ock/pdb |
| Descriptor | 3C-like proteinase nsp5, 2-fluoro-N-(isoquinolin-4-yl)-5-(trifluoromethyl)benzamide, SODIUM ION, ... (4 entities in total) |
| Functional Keywords | hydrolase |
| Biological source | Severe acute respiratory syndrome coronavirus 2 |
| Total number of polymer chains | 1 |
| Total formula weight | 34182.80 |
| Authors | Knapp, M.S.,Ornelas, E. (deposition date: 2025-04-24, release date: 2026-02-18, Last modification date: 2026-03-11) |
| Primary citation | Papillon, J.P.N.,Yuan, J.,Hesse, M.J.,Zhang, L.,Robinson, R.I.,Ware, N.F.,Hornak, V.,Karki, R.G.,Kirrane, T.,Garland, K.,Joseph, S.,Moquin, S.A.,Lakshminarayana, S.B.,Tandeske, L.,Dovala, D.,Knapp, M.,Ornelas, E.,Fuller, D.,Ho, P.I.,Xie, X.,Vulic, K.,Skolnik, S.M.,Gao, J.,Zambrowski, M.,Spiess, M.,Duca, J.S.,Busby, S.A.,Schirle, M.,Robinson, M.,Shi, P.Y.,Moser, H.E.,Sarko, C.,Bradner, J.E.,Diagana, T.T.,Tallarico, J.A. Discovery of EGT710, an Oral Nonpeptidomimetic Reversible Covalent SARS-CoV-2 Main Protease Inhibitor. J.Med.Chem., 69:3868-3886, 2026 Cited by PubMed Abstract: The coronavirus main protease (3CL, M, nsp5) is a highly conserved cysteine protease unique to the Coronaviridae family, including SARS-CoV-2, and is a validated target for the treatment of COVID-19. Our efforts focused on the identification of a nonpeptidomimetic M inhibitor, due to the potential for superior pharmacological properties. Herein, we report our efforts leveraging virtual screening and X-ray crystallography that enabled a structure-based drug design approach, leading to the discovery of series of quinazoline-2,4(1,3)-dione and oxoimidazolidine-4-carbonitrile compounds with potent inhibition of SARS-CoV-2 M as well as other coronaviruses main proteases. Extensive lead optimization focusing on pharmacokinetic properties, developability, and breadth of activity across coronaviruses, led to the identification of . demonstrates excellent potency against SARS-CoV-2 infection in a primary differentiated normal human bronchial epithelial (dNHBE) cellular assay, as well as a favorable pharmacology profile that supported advancement into preclinical and clinical studies. PubMed: 41663073DOI: 10.1021/acs.jmedchem.5c02360 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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