7E18
Crystal structure of SAR-CoV-2 3CL protease complex with inhibitor YH-53
Summary for 7E18
| Entry DOI | 10.2210/pdb7e18/pdb |
| Descriptor | Replicase polyprotein 1ab, N-[(2S)-1-[[(2S)-1-(1,3-benzothiazol-2-yl)-1-oxidanylidene-3-[(3S)-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]-4-methoxy-1H-indole-2-carboxamide, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | sars-cov-2 3cl protease, hydrolase |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) |
| Total number of polymer chains | 1 |
| Total formula weight | 34835.70 |
| Authors | Senda, M.,Konno, S.,Hayashi, Y.,Senda, T. (deposition date: 2021-02-01, release date: 2021-06-23, Last modification date: 2023-11-29) |
| Primary citation | Konno, S.,Kobayashi, K.,Senda, M.,Funai, Y.,Seki, Y.,Tamai, I.,Schakel, L.,Sakata, K.,Pillaiyar, T.,Taguchi, A.,Taniguchi, A.,Gutschow, M.,Muller, C.E.,Takeuchi, K.,Hirohama, M.,Kawaguchi, A.,Kojima, M.,Senda, T.,Shirasaka, Y.,Kamitani, W.,Hayashi, Y. 3CL Protease Inhibitors with an Electrophilic Arylketone Moiety as Anti-SARS-CoV-2 Agents. J.Med.Chem., 65:2926-2939, 2022 Cited by PubMed Abstract: The novel coronavirus, SARS-CoV-2, has been identified as the causative agent for the current coronavirus disease (COVID-19) pandemic. 3CL protease (3CL) plays a pivotal role in the processing of viral polyproteins. We report peptidomimetic compounds with a unique benzothiazolyl ketone as a warhead group, which display potent activity against SARS-CoV-2 3CL. The most potent inhibitor YH-53 can strongly block the SARS-CoV-2 replication. X-ray structural analysis revealed that YH-53 establishes multiple hydrogen bond interactions with backbone amino acids and a covalent bond with the active site of 3CL. Further results from computational and experimental studies, including an absorption, distribution, metabolism, and excretion profile, pharmacokinetics, and metabolic analysis of YH-53 suggest that it has a high potential as a lead candidate to compete with COVID-19. PubMed: 34313428DOI: 10.1021/acs.jmedchem.1c00665 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
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