8DZB
Crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with inhibitor 11
Summary for 8DZB
| Entry DOI | 10.2210/pdb8dzb/pdb |
| Descriptor | 3C-like proteinase nsp5, GLYCEROL, benzyl {(3S)-1-[(2S)-1-({(2S,3R)-4-(cyclopropylamino)-3-hydroxy-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}amino)-4-methyl-1-oxopentan-2-yl]-5-oxopyrrolidin-3-yl}carbamate, ... (4 entities in total) |
| Functional Keywords | covid, covid19, covid-19, sars, sars cov2, cov, ncov 19, coronavirus, main protease, 3cl, mpro, pro, gc376, calpain inhibitor ii, leupeptin, calpain, aldehyde, gc-376, 3cl-like, a-ketoamide, alpheketoamide, alpha, ketoamide, petidometic, protease, cysteine, hydrolase-hydrolase inhibitor complex, viral protein-inhibitor complex, viral protein/inhibitor |
| Biological source | Severe acute respiratory syndrome coronavirus 2 |
| Total number of polymer chains | 1 |
| Total formula weight | 34489.31 |
| Authors | |
| Primary citation | Wang, L.,Ma, C.,Sacco, M.D.,Xue, S.,Mahmoud, M.,Calcul, L.,Chen, Y.,Wang, J.,Cai, J. Development of the Safe and Broad-Spectrum Aldehyde and Ketoamide Mpro inhibitors Derived from the Constrained alpha , gamma-AA Peptide Scaffold. Chemistry, 29:e202300476-e202300476, 2023 Cited by PubMed Abstract: SARS-CoV-2 is still wreaking havoc all over the world with surging morbidity and high mortality. The main protease (M ) is essential in the replication of SARS-CoV-2, enabling itself an active target for antiviral development. Herein, we reported the design and synthesis of a new class of peptidomimetics-constrained α, γ-AA peptides, based on which a series of aldehyde and ketoamide inhibitors of the M of SARS-CoV-2 were prepared. The lead compounds showed excellent inhibitory activity in the FRET-based M enzymatic assay not only for the M of SARS-CoV-2 but also for SARS-CoV and MERS-CoV, along with HCoVs like HCoV-OC43, HCoV-229E, HCoV-NL63 and HKU1. The X-ray crystallographic results demonstrated that our compounds form a covalent bond with the catalytic Cys145. They also demonstrated effective antiviral activity against live SARS-CoV-2. Overall, the results suggest that α, γ-AA peptide could be a promising molecular scaffold in designing novel M inhibitors of SARS-CoV-2 and other coronaviruses. PubMed: 36920943DOI: 10.1002/chem.202300476 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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