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Updated: May 29, 2026

Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses
11:48

Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses

Published on: April 4, 2019

Double-Stapled Peptide Scan Yields Potent Fusion Inhibitors of Respiratory Syncytial Virus

Nadège Pidoux1, Logan Roh1, Nancy Nicolet1

  • 1HES-SO Valais-Wallis, Institute of Life Sciences, HES-SO University of Applied Sciences Western and Arts Switzerland, rue de l'Industrie 19, Sion 1950, Switzerland.

Journal of Medicinal Chemistry
|May 27, 2026
PubMed

Insights

New stapled peptides show potent inhibition against respiratory syncytial virus (RSV) fusion, offering a promising therapeutic strategy. These peptides are effective even against resistant viral strains and can be delivered intranasally to the lungs.

Area of Science:

  • Virology
  • Structural Biology
  • Drug Discovery

Background:

  • Respiratory syncytial virus (RSV) poses a significant global health threat, especially to infants and the elderly.
  • Current treatments for RSV are limited, necessitating the development of novel therapeutic agents.

Purpose of the Study:

  • To identify and characterize novel peptide inhibitors of RSV fusion.
  • To evaluate the antiviral activity and delivery potential of these peptides.

Main Methods:

  • Screening of double-stapled peptides derived from the RSV F heptad repeat.
  • Structural activity relationship (SAR) analysis and X-ray crystallography.
  • In vivo pharmacokinetic, imaging, and feasibility studies in RSV-infected mice.

Main Results:

  • Identified three potent RSV fusion inhibitors: 3/4i, 3/4m, and 4/4g.
  • These peptides demonstrated activity against RSV escape mutants resistant to small-molecule inhibitors.
  • X-ray crystallography revealed strong hydrophobic interactions contributing to the potency of 3/4i and 3/4m.
  • Intranasal administration was found to be a feasible delivery route to the lungs in a mouse model.

Conclusions:

  • Double-stapled peptides are effective inhibitors of RSV fusion.
  • These peptides offer a potential therapeutic strategy against RSV, including resistant strains.
  • Intranasal delivery of these stapled peptides to the lungs is a promising approach for RSV treatment.

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