7COM
Crystal structure of the SARS-CoV-2 main protease in complex with Boceprevir (space group P212121)
Summary for 7COM
| Entry DOI | 10.2210/pdb7com/pdb |
| Related | 7C7P |
| Related PRD ID | PRD_002382 |
| Descriptor | 3C-like proteinase, boceprevir (bound form) (3 entities in total) |
| Functional Keywords | coronavirus, protease, inhibitor, complex, viral protein., viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) |
| Total number of polymer chains | 2 |
| Total formula weight | 68694.48 |
| Authors | Zeng, R.,Qiao, J.X.,Wang, Y.F.,Li, Y.S.,Yao, R.,Liu, J.M.,Zhou, Y.L.,Chen, P.,Yang, S.Y.,Lei, J. (deposition date: 2020-08-04, release date: 2020-08-19, Last modification date: 2024-11-06) |
| Primary citation | Qiao, J.,Li, Y.S.,Zeng, R.,Liu, F.L.,Luo, R.H.,Huang, C.,Wang, Y.F.,Zhang, J.,Quan, B.,Shen, C.,Mao, X.,Liu, X.,Sun, W.,Yang, W.,Ni, X.,Wang, K.,Xu, L.,Duan, Z.L.,Zou, Q.C.,Zhang, H.L.,Qu, W.,Long, Y.H.,Li, M.H.,Yang, R.C.,Liu, X.,You, J.,Zhou, Y.,Yao, R.,Li, W.P.,Liu, J.M.,Chen, P.,Liu, Y.,Lin, G.F.,Yang, X.,Zou, J.,Li, L.,Hu, Y.,Lu, G.W.,Li, W.M.,Wei, Y.Q.,Zheng, Y.T.,Lei, J.,Yang, S. SARS-CoV-2 M pro inhibitors with antiviral activity in a transgenic mouse model. Science, 371:1374-1378, 2021 Cited by PubMed Abstract: The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (M) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing M inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 M activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of M in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats. PubMed: 33602867DOI: 10.1126/science.abf1611 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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