29QJ
Respiratory syncytial virus fusion protein N-terminal heptad repeat domain in complex with Double stapled peptide 4/4g
Summary for 29QJ
| Entry DOI | 10.2210/pdb29qj/pdb |
| Descriptor | Fusion glycoprotein F1, Double stapled peptide 4/4g (3 entities in total) |
| Functional Keywords | human respiratory syncytial virus, fusion protein, fusion inhibitor, stapled peptide, six helix bundle, complex, antiviral protein, viral protein |
| Biological source | Human respiratory syncytial virus A More |
| Total number of polymer chains | 2 |
| Total formula weight | 8028.50 |
| Authors | |
| Primary citation | Pidoux, N.,Roh, L.,Nicolet, N.,Marti, R.,Le Rouzic, A.,Prompt, C.,Fix, J.,Duquerroy, S.,Rey, F.,Rameix-Welti, M.A.,Keck, M.,Barbe, P.,Garcin, D.,Mottet-Osman, G.,Larcher, T.,Galloux, M.,Nyanguile, O. Double-Stapled Peptide Scan Yields Potent Fusion Inhibitors of Respiratory Syncytial Virus. J.Med.Chem., 2026 Cited by PubMed Abstract: Respiratory syncytial virus infection (RSV) is a major global health concern, particularly in infants and elderly populations. In this work, we have screened and identified 3 double-stapled peptides derived from a minimal domain of the RSV F heptad repeat, namely , , and , which are potent inhibitors of RSV fusion and remain active against viral escape mutants resistant to small-molecule fusion inhibitors. Our structural activity relationship (SAR) analysis demonstrates that combining a limited set of staples is sufficient to achieve high antiviral potency. X-ray crystallography revealed that the enhanced potency of and primarily arises from strong hydrophobic interactions between the N-terminal staple and the trimeric HR1 coiled coil of RSV F. pharmacokinetic, imaging, and feasibility studies in RSV-infected Balb/c mice further support intranasal administration as a promising route for delivering these stapled peptides to the lung, highlighting their potential as therapeutics against RSV. PubMed: 42203199DOI: 10.1021/acs.jmedchem.5c02932 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.325 Å) |
Structure validation
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