9MDQ
Crystal Structure of SARS-CoV-2 Omicron Main Protease (Mpro) Complex with Azapeptide Inhibitor 20a
This is a non-PDB format compatible entry.
Summary for 9MDQ
| Entry DOI | 10.2210/pdb9mdq/pdb |
| Descriptor | 3C-like proteinase nsp5, N-[(2S)-1-{2-(dichloroacetyl)-2-[(2-oxo-1,2-dihydropyridin-3-yl)methyl]hydrazin-1-yl}-4-methyl-1-oxopentan-2-yl]-4-methoxy-1H-indole-2-carboxamide (3 entities in total) |
| Functional Keywords | sars-cov-2, mpro, main protease, 3clpro, nsp5, inhibitor, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 |
| Total number of polymer chains | 1 |
| Total formula weight | 34402.99 |
| Authors | Vishwakarma, J.,Taylor, A.B.,Harris, R.S. (deposition date: 2024-12-05, release date: 2025-09-24, Last modification date: 2025-10-08) |
| Primary citation | Flury, P.,Vishwakarma, J.,Sylvester, K.,Higashi-Kuwata, N.,Dabrowska, A.K.,Delgado, R.,Cuell, A.,Basu, R.,Taylor, A.B.,de Oliveira, E.G.,Magalhaes Serafim, M.S.,Qiao, J.,Chen, Y.,Yang, S.,O'Donoghue, A.J.,Mitsuya, H.,Gutschow, M.,Laufer, S.A.,Muller, C.E.,Harris, R.S.,Pillaiyar, T. Azapeptide-Based SARS-CoV-2 Main Protease Inhibitors: Design, Synthesis, Enzyme Inhibition, Structural Determination, and Antiviral Activity. J.Med.Chem., 68:19339-19376, 2025 Cited by PubMed Abstract: M of SARS-CoV-2 plays a vital role in the replication and pathogenesis of virus. Additionally, its high conservation within the family makes it an attractive therapeutic target for developing broad-spectrum agents. This study describes the design, synthesis, and structure-activity relationships of azapeptide-based SARS-CoV-2 M inhibitors, leading to several compounds with nanomolar IC values. Examples include (IC = 13.3 nM), (IC = 30.6 nM), (, IC = 28.0 nM), and (IC = 30.4 nM). Some compounds inhibit MERS-CoV and SARS-CoV-1 M but not the human protease cathepsin L. Several inhibitors, such as and , exhibit antiviral activity with potencies comparable to nirmatrelvir and activity against the E166V-carrying SARS-CoV-2 variant (SARS-CoV-2). An M cocrystal structure with shows a covalent adduct with the catalytic Cys145. Overall, these new inhibitors are promising chemical tools that may contribute to the identification of future pan-anticoronaviral drugs. PubMed: 40932417DOI: 10.1021/acs.jmedchem.5c01520 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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