8ZT9
The Crystal structure of mol066 bound to the main protease (3CLpro/Mpro) of SARS-CoV-2
This is a non-PDB format compatible entry.
Summary for 8ZT9
| Entry DOI | 10.2210/pdb8zt9/pdb |
| Descriptor | 3C-like proteinase, 6-[(6-chloranyl-2-propan-2-yl-indazol-5-yl)amino]-3-[(1-methyl-1,2,4-triazol-3-yl)methyl]-1-[[2,4,5-tris(fluoranyl)phenyl]methyl]pyrimidine-2,4-dione, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | inhibitor, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) |
| Total number of polymer chains | 2 |
| Total formula weight | 68002.11 |
| Authors | |
| Primary citation | Pan, F.,Zhou, Q.,Yan, M.,Yang, S.,Hu, R.,Chen, Y.,Wen, Y.,Chao, Y.,Xie, C.,Ou, W.,Li, Y.,Zhang, H.,Guo, D.,Zhang, X. Development of pyrimidone derivatives as nonpeptidic and noncovalent 3-chymotrypsin-like protease (3CL pro ) inhibitors with anti-coronavirus activities. Bioorg.Chem., 154:107988-107988, 2025 Cited by PubMed Abstract: 3CL is crucial to the life cycle of SARS-CoV-2 and exhibits high sequence similarity with other coronaviruses, while being absent in human proteases. This makes it an ideal target for developing broad-spectrum antiviral drugs. Ensitrelvir (S-217622) is the only launched non-covalent, non-peptidomimetic 3CL inhibitor, offering certain advantages in terms of dosage and metabolism. Using S-217622 as the lead, we designed and synthesized 43 pyrimidone derivatives and conducted a systematic evaluation of their structure-activity relationships. Among them, A36 exhibited strong inhibitory activity against several β-coronaviruses and demonstrated low cytotoxicity. A36 also displayed moderate stability in mouse liver microsomes. Co-crystal structure analysis of 3CL in complex with A36 revealed the similar binding mode with S-217622. A36 shows strong potential as a promising lead for broad-spectrum anti-coronavirus therapy, warranting further investigation. PubMed: 39591689DOI: 10.1016/j.bioorg.2024.107988 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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