9RA5
Respiratory syncytial virus fusion protein N-terminal heptad repeat domain in complex with Double stapled peptide 3/4i
Summary for 9RA5
| Entry DOI | 10.2210/pdb9ra5/pdb |
| Descriptor | Fusion glycoprotein F1, Double stapled peptide 3/4i, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | human respiratory syncytial virus, fusion protein, fusion inhibitor, stapled peptide, six helix bundle, complex, antiviral protein |
| Biological source | Human respiratory syncytial virus A More |
| Total number of polymer chains | 2 |
| Total formula weight | 8043.59 |
| Authors | Duquerroy, S.,Nyanguile, O.,Gsponer, N.,Nicolet, N.,Marti, R. (deposition date: 2025-05-20, release date: 2026-06-03, Last modification date: 2026-06-24) |
| 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., 69:12910-12924, 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 (1.625 Å) |
Structure validation
Download full validation report
