8VDJ
Crystal structure of SARS-CoV-2 3CL protease (3CLpro) as a covalent complex with EDP-235
This is a non-PDB format compatible entry.
Summary for 8VDJ
| Entry DOI | 10.2210/pdb8vdj/pdb |
| Descriptor | 3C-like proteinase nsp5, 4,6,7-trifluoro-N-{(2S)-1-[(3R,5'R)-5'-(iminomethyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidin]-1'-yl]-4-methyl-1-oxopentan-2-yl}-N-methyl-1H-indole-2-carboxamide, THIOCYANATE ION, ... (4 entities in total) |
| Functional Keywords | 3c-like proteinase sars-cov-2, viral protein, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2, 2019-nCoV, COVID-19 virus) |
| Total number of polymer chains | 2 |
| Total formula weight | 68788.27 |
| Authors | Cade, I.A.,Rhodin, M.H.J. (deposition date: 2023-12-15, release date: 2024-08-14, Last modification date: 2024-11-13) |
| Primary citation | Rhodin, M.H.J.,Reyes, A.C.,Balakrishnan, A.,Bisht, N.,Kelly, N.M.,Gibbons, J.S.,Lloyd, J.,Vaine, M.,Cressey, T.,Crepeau, M.,Shen, R.,Manalo, N.,Castillo, J.,Levene, R.E.,Leonard, D.,Zang, T.,Jiang, L.,Daniels, K.,Cox, R.M.,Lieber, C.M.,Wolf, J.D.,Plemper, R.K.,Leist, S.R.,Scobey, T.,Baric, R.S.,Wang, G.,Goodwin, B.,Or, Y.S. The small molecule inhibitor of SARS-CoV-2 3CLpro EDP-235 prevents viral replication and transmission in vivo. Nat Commun, 15:6503-6503, 2024 Cited by PubMed Abstract: The COVID-19 pandemic has led to the deaths of millions of people and severe global economic impacts. Small molecule therapeutics have played an important role in the fight against SARS-CoV-2, the virus responsible for COVID-19, but their efficacy has been limited in scope and availability, with many people unable to access their benefits, and better options are needed. EDP-235 is specifically designed to inhibit the SARS-CoV-2 3CLpro, with potent nanomolar activity against all SARS-CoV-2 variants to date, as well as clinically relevant human and zoonotic coronaviruses. EDP-235 maintains potency against variants bearing mutations associated with nirmatrelvir resistance. Additionally, EDP-235 demonstrates a ≥ 500-fold selectivity index against multiple host proteases. In a male Syrian hamster model of COVID-19, EDP-235 suppresses SARS-CoV-2 replication and viral-induced hamster lung pathology. In a female ferret model, EDP-235 inhibits production of SARS-CoV-2 infectious virus and RNA at multiple anatomical sites. Furthermore, SARS-CoV-2 contact transmission does not occur when naïve ferrets are co-housed with infected, EDP-235-treated ferrets. Collectively, these results demonstrate that EDP-235 is a broad-spectrum coronavirus inhibitor with efficacy in animal models of primary infection and transmission. PubMed: 39090095DOI: 10.1038/s41467-024-50931-8 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.002 Å) |
Structure validation
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