7TUU
Structure of the SARS-CoV-2 main protease in complex with halicin
Summary for 7TUU
| Entry DOI | 10.2210/pdb7tuu/pdb |
| Descriptor | 3C-like proteinase nsp5, 5-nitro-1,3-thiazole (3 entities in total) |
| Functional Keywords | main protease, viral protein, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Severe acute respiratory syndrome coronavirus 2 |
| Total number of polymer chains | 1 |
| Total formula weight | 34215.92 |
| Authors | Yang, K.S.,Liu, W.R. (deposition date: 2022-02-03, release date: 2022-08-03, Last modification date: 2024-11-20) |
| Primary citation | Yang, K.S.,Alex Kuo, S.T.,Blankenship, L.R.,Geng, Z.Z.,Li, S.G.,Russell, D.H.,Yan, X.,Xu, S.,Liu, W.R. Repurposing Halicin as a potent covalent inhibitor for the SARS-CoV-2 main protease. Curr Res Chem Biol, 2:100025-100025, 2022 Cited by PubMed Abstract: The rapid spread of COVID-19 has caused a worldwide public health crisis. For prompt and effective development of antivirals for SARS-CoV-2, the pathogen of COVID-19, drug repurposing has been broadly conducted by targeting the main protease (M), a key enzyme responsible for the replication of virus inside the host. In this study, we evaluate the inhibition potency of a nitrothiazole-containing drug, halicin, and reveal its reaction and interaction mechanism with M. The potency test shows that halicin inhibits the activity of M an IC of 181.7 nM. Native mass spectrometry and X-ray crystallography studies clearly indicate that the nitrothiazole fragment of halicin covalently binds to the catalytic cysteine C145 of M. Interaction and conformational changes inside the active site of M suggest a favorable nucleophilic aromatic substitution reaction mechanism between M C145 and halicin, explaining the high inhibition potency of halicin towards M. PubMed: 35815070DOI: 10.1016/j.crchbi.2022.100025 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
Download full validation report
