9MVL
Co-crystal structure of feline coronavirus UU23 main protease with GC376
Summary for 9MVL
| Entry DOI | 10.2210/pdb9mvl/pdb |
| Descriptor | Peptidase C30, (1R,2S)-2-({N-[(benzyloxy)carbonyl]-L-leucyl}amino)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonic acid (3 entities in total) |
| Functional Keywords | mpro, uu23, feline coronavirus, viral protein, main protease, gc376, feline enteric coronavirus, alpha coronavirus |
| Biological source | Feline coronavirus UU23 |
| Total number of polymer chains | 1 |
| Total formula weight | 33300.74 |
| Authors | Shaqra, A.M.,Maryam, A.,Schiffer, C.A. (deposition date: 2025-01-15, release date: 2025-11-26, Last modification date: 2025-12-10) |
| Primary citation | Maryam, A.,Moquin, S.A.,Dovala, D.,Kaur, J.,Kurt Yilmaz, N.,Shaqra, A.M.,Schiffer, C.A. Structural Analysis of Inhibitor Binding to the Feline Enteric Coronavirus (FECV) Main Protease. Viruses, 17:-, 2025 Cited by PubMed Abstract: Coronaviruses include various strains that reside in natural animal reservoirs, with zoonotic transmission posing risks to both domesticated animals and human health. Recent efforts to address coronavirus infections have focused on developing inhibitors targeting the main protease (M), some of which exhibit potential broad-spectrum efficacy. This study presents crystal structures of four clinically relevant inhibitors-GC376, PF-00835231, nirmatrelvir, and ibuzatrelvir-bound to M from the feline coronavirus strain FECV-UU23. Structural analysis identified distinct FECV-specific features within the active site where these inhibitors bind and revealed S4 loop as a susceptible structural region essential for the enhanced binding of inhibitors in UU23 M. We therefore propose to incorporate sterically constrained, functionally tailored heterocyclic moieties at the P3 site of known inhibitors which can optimally engage Q187, P188, and S189 residues of the S4 loop. The findings presented enhance understanding of inhibitor specificity and reinforce the promise of these inhibitor scaffolds for developing antivirals against feline coronavirus strains, with possible applications in broad-spectrum coronavirus therapy. PubMed: 41305527DOI: 10.3390/v17111506 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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