7NTS
Crystal structure of the SARS-CoV-2 Main Protease with oxidized C145
Summary for 7NTS
| Entry DOI | 10.2210/pdb7nts/pdb |
| Related | 7NTQ 7NTT 7NTW |
| Descriptor | Replicase polyprotein 1ab, DIMETHYL SULFOXIDE, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | 3clpro, main protease, sars-cov-2, 2019-ncov, cso, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) |
| Total number of polymer chains | 1 |
| Total formula weight | 34738.53 |
| Authors | Dupre, E.,Villeret, V.,Hanoulle, X. (deposition date: 2021-03-10, release date: 2021-10-06, Last modification date: 2024-11-13) |
| Primary citation | Cantrelle, F.X.,Boll, E.,Brier, L.,Moschidi, D.,Belouzard, S.,Landry, V.,Leroux, F.,Dewitte, F.,Landrieu, I.,Dubuisson, J.,Deprez, B.,Charton, J.,Hanoulle, X. NMR Spectroscopy of the Main Protease of SARS-CoV-2 and Fragment-Based Screening Identify Three Protein Hotspots and an Antiviral Fragment. Angew.Chem.Int.Ed.Engl., 60:25428-25435, 2021 Cited by PubMed Abstract: The main protease (3CLp) of the SARS-CoV-2, the causative agent for the COVID-19 pandemic, is one of the main targets for drug development. To be active, 3CLp relies on a complex interplay between dimerization, active site flexibility, and allosteric regulation. The deciphering of these mechanisms is a crucial step to enable the search for inhibitors. In this context, using NMR spectroscopy, we studied the conformation of dimeric 3CLp from the SARS-CoV-2 and monitored ligand binding, based on NMR signal assignments. We performed a fragment-based screening that led to the identification of 38 fragment hits. Their binding sites showed three hotspots on 3CLp, two in the substrate binding pocket and one at the dimer interface. F01 is a non-covalent inhibitor of the 3CLp and has antiviral activity in SARS-CoV-2 infected cells. This study sheds light on the complex structure-function relationships of 3CLp and constitutes a strong basis to assist in developing potent 3CLp inhibitors. PubMed: 34570415DOI: 10.1002/anie.202109965 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.477 Å) |
Structure validation
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