8ZBP
The crystal structure of SARS-CoV-2 main protease in complex with chebulagic acid (CHLA)
This is a non-PDB format compatible entry.
Summary for 8ZBP
| Entry DOI | 10.2210/pdb8zbp/pdb |
| Descriptor | 3C-like proteinase nsp5, 2-[(4R,5S,7R,25S,26R,29R,30S,31R)-13,14,15,18,19,20,21,31,35,36-decahydroxy-2,10,23,28,32-pentaoxo-5-(3,4,5-trihydroxybenzoyl)oxy-3,6,9,24,27,33-hexaoxaheptacyclo[28.7.1.04,25.07,26.011,16.017,22.034,38]octatriaconta-1(37),11,13,15,17(22),18,20,34(38),35-nonaen-29-yl]acetic acid, DIMETHYL SULFOXIDE, ... (4 entities in total) |
| Functional Keywords | sars-cov-2, main protease, 3clpro, mpro, viral protease, compound zm_097, hydrolase, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) |
| Total number of polymer chains | 1 |
| Total formula weight | 34858.34 |
| Authors | |
| Primary citation | Zhang, M.,Wang, C.,Feng, L.,Yang, Q.,Cao, Y.,Zhao, Y.,Zhang, J.,Wang, Y.,Rao, Z.,Zhang, B. Targeting SARS-CoV-2 main protease for the discovery of a broad-spectrum COVID-19 inhibitor by intensive multi-tiered validation. Acta Pharm Sin B, 15:5789-5802, 2025 Cited by PubMed Abstract: SARS-CoV-2 and its emerging variants continue to pose a significant global public health threat. The SARS-CoV-2 main protease (M) is a critical target for the development of antiviral agents that can inhibit viral replication and transcription. In this study, we identified chebulagic acid (CHLA), isolated from Retz., as a potent non-peptidomimetic and non-covalent M inhibitor. CHLA exhibited intermolecular interactions and provided significant protection to Vero E6 cells against a range of SARS-CoV-2 variants, including the wild-type, Delta, Omicron BA.1.1, BA.2.3, BA.4, and BA.5, with EC values below 2 μmol/L. Moreover, studies confirmed the antiviral efficacy of CHLA in K18-hACE2 mice. Notably, CHLA bound to a unique groove at the interface between M domains I and II, which was revealed by the high-resolution crystal structure (1.4 Å) of the M-CHLA complex, shrinking the substrate binding pocket of M and inducing M aggregation. CHLA was proposed to act as an allosteric inhibitor. Pharmacokinetic profiling and safety assessments underscore CHLA's potential as a promising broad-spectrum antiviral candidate. These findings report a novel binding site on M and identify antiviral activity of CHLA, providing a robust framework for lead compounds discovery and elucidating the underlying molecular mechanisms of inhibition. PubMed: 41311409DOI: 10.1016/j.apsb.2025.09.033 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.41 Å) |
Structure validation
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