9IK2
The co-crystal structure of SARS-CoV-2 Mpro in complex with compound H109
This is a non-PDB format compatible entry.
Summary for 9IK2
| Entry DOI | 10.2210/pdb9ik2/pdb |
| Descriptor | 3C-like proteinase, tert-butyl N-[(2S)-1-[[(2S)-1-[[(2S)-1-azanylidene-3-[(3S)-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]amino]-1-oxidanylidene-3-phenyl-propan-2-yl]amino]-3,3-dimethyl-1-oxidanylidene-butan-2-yl]carbamate (3 entities in total) |
| Functional Keywords | sars-cov-2 main protease, inhibitor, complex, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) |
| Total number of polymer chains | 1 |
| Total formula weight | 34341.19 |
| Authors | Feng, Y.,Zheng, W.Y.,Han, P.,Fu, L.F.,Qi, J.X. (deposition date: 2024-06-26, release date: 2024-07-31, Last modification date: 2025-11-26) |
| Primary citation | Yuan, S.,Wang, J.,Sang, X.,Xie, Y.,Feng, Y.,Poon, V.K.M.,Chan, C.C.S.,Tsang, J.O.L.,Chik, K.K.H.,Zhou, J.,Xu, Y.,Han, P.,Zheng, W.,Fu, L.,Huang, L.S.M.,Wu, M.,An, J.,Yuen, K.Y.,Qi, J.,Huang, Z.,Chan, J.F.W. Structure-guided discovery of a small molecule inhibitor of SARS-CoV-2 main protease with potent in vitro and in vivo antiviral activities. J.Virol., :e0100125-e0100125, 2025 Cited by PubMed Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M) is a clinically validated target for the treatment of coronavirus disease 2019 (COVID-19). Here, we report the hit-to-lead discovery of a new nitrile-based inhibitor, , of SARS-CoV-2 M from a series of chemical modifications of a nitrile-warhead-containing compound guided by its 1.8 Å high-resolution crystal structure in complex with SARS-CoV-2 M. exhibited potent and selective inhibition of SARS-CoV-2 M with IC of 12.7 nM and exerted broad anti-SARS-CoV-2 activity in VeroE6-TMPRSS2 cells. Furthermore, -treated golden Syrian hamsters demonstrated significantly lower respiratory tract viral burden compared with solvent-treated control hamsters. may serve as a new lead for developing antiviral therapeutics for SARS-CoV-2 infection.IMPORTANCEIn this study, a structure-guided hit-to-lead strategy was employed to develop a nanomolar potent small molecule inhibitor H135 of SARS-CoV-2 M with strong anti-SARS-CoV-2 infection activity in cell cultures and animals. H135 may serve as a new lead for developing antiviral agents targeting the virus's main protease M. PubMed: 41236503DOI: 10.1128/jvi.01001-25 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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