6XHM
Covalent complex of SARS-CoV-2 main protease with N-[(2S)-1-({(2S,3S)-3,4-dihydroxy-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}amino)-4-methyl-1-oxopentan-2-yl]-4-methoxy-1H-indole-2-carboxamide
Summary for 6XHM
| Entry DOI | 10.2210/pdb6xhm/pdb |
| Descriptor | 3C-like proteinase, N-[(2S)-1-({(2S,3S)-3,4-dihydroxy-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}amino)-4-methyl-1-oxopentan-2-yl]-4-methoxy-1H-indole-2-carboxamide, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | coronavirus protease inhibitor complex, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) |
| Total number of polymer chains | 2 |
| Total formula weight | 68662.26 |
| Authors | Gajiwala, K.S.,Ferre, R.A.,Ryan, K.,Stewart, A.E. (deposition date: 2020-06-19, release date: 2020-07-08, Last modification date: 2024-10-16) |
| Primary citation | Hoffman, R.L.,Kania, R.S.,Brothers, M.A.,Davies, J.F.,Ferre, R.A.,Gajiwala, K.S.,He, M.,Hogan, R.J.,Kozminski, K.,Li, L.Y.,Lockner, J.W.,Lou, J.,Marra, M.T.,Mitchell Jr., L.J.,Murray, B.W.,Nieman, J.A.,Noell, S.,Planken, S.P.,Rowe, T.,Ryan, K.,Smith 3rd, G.J.,Solowiej, J.E.,Steppan, C.M.,Taggart, B. Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19. J.Med.Chem., 63:12725-12747, 2020 Cited by PubMed Abstract: The novel coronavirus disease COVID-19 that emerged in 2019 is caused by the virus SARS CoV-2 and named for its close genetic similarity to SARS CoV-1 that caused severe acute respiratory syndrome (SARS) in 2002. Both SARS coronavirus genomes encode two overlapping large polyproteins, which are cleaved at specific sites by a 3C-like cysteine protease (3CL) in a post-translational processing step that is critical for coronavirus replication. The 3CL sequences for CoV-1 and CoV-2 viruses are 100% identical in the catalytic domain that carries out protein cleavage. A research effort that focused on the discovery of reversible and irreversible ketone-based inhibitors of SARS CoV-1 3CL employing ligand-protease structures solved by X-ray crystallography led to the identification of and . Preclinical experiments reveal () as a potent inhibitor of CoV-2 3CL with suitable pharmaceutical properties to warrant further development as an intravenous treatment for COVID-19. PubMed: 33054210DOI: 10.1021/acs.jmedchem.0c01063 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.406 Å) |
Structure validation
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