Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Mucosal delivery of a double-stapled RSV peptide prevents nasopulmonary infection
Gregory H. Bird, … , Shyam S. Mohapatra, Loren D. Walensky
Gregory H. Bird, … , Shyam S. Mohapatra, Loren D. Walensky
Published April 17, 2014
Citation Information: J Clin Invest. 2014;124(5):2113-2124. https://doi.org/10.1172/JCI71856.
View: Text | PDF
Research Article

Mucosal delivery of a double-stapled RSV peptide prevents nasopulmonary infection

  • Text
  • PDF
Abstract

Respiratory syncytial virus (RSV) infection accounts for approximately 64 million cases of respiratory disease and 200,000 deaths worldwide each year, yet no broadly effective prophylactic or treatment regimen is available. RSV deploys paired, self-associating, heptad repeat domains of its fusion protein, RSV-F, to form a fusogenic 6-helix bundle that enables the virus to penetrate the host cell membrane. Here, we developed hydrocarbon double-stapled RSV fusion peptides that exhibit stabilized α-helical structure and striking proteolytic resistance. Pretreatment with double-stapled RSV peptides that specifically bound to the RSV fusion bundle inhibited infection by both laboratory and clinical RSV isolates in cells and murine infection models. Intranasal delivery of a lead double-stapled RSV peptide effectively prevented viral infection of the nares. A chitosan-based nanoparticle preparation markedly enhanced pulmonary delivery, further preventing progression of RSV infection to the lung. Thus, our results provide a strategy for inhibiting RSV infection by mucosal and endotracheal delivery of double-stapled RSV fusion peptides.

Authors

Gregory H. Bird, Sandhya Boyapalle, Terianne Wong, Kwadwo Opoku-Nsiah, Raminder Bedi, W. Christian Crannell, Alisa F. Perry, Huy Nguyen, Viviana Sampayo, Ankita Devareddy, Subhra Mohapatra, Shyam S. Mohapatra, Loren D. Walensky

×

Figure 3

Inhibition of RSV infection and syncytia formation by i,i+7–stapled SAH-RSVF peptides.

Options: View larger image (or click on image) Download as PowerPoint
Inhibition of RSV infection and syncytia formation by i,i+7–stapled SAH-...
(A) The capacity of SAH-RSVF peptides to suppress infection of A549 cells by GFP-expressing rgRSV correlated with their competitive binding potency in the 5-HB FP assay (see Figure 1D and Figure 2C). SAH-RSVFB, SAH-RSVFC, SAH-RSVFD, SAH-RSVFBD, and SAH-RSVFCD demonstrated the most robust viral inhibitory activity, whereas controls SAH-RSVFF, SAH-RSVFBF, and SAH-RSVFCF were markedly impaired. Data represent mean ± SEM for experiments performed in triplicate. (B) Comparative activity of SAH-RSVF peptides in inhibiting syncytia formation after rgRSV infection of A549 cells, as counted in 3 different wells at 4 discrete locations per well at 48 hours after infection. Data are mean ± SEM. (C) Inhibition of RSV-A2 infection by SAH-RSVF peptides, as assessed by HEp-2 cell plaque assay and measurement of viral titers (pfu/ml). Data are mean ± SEM for 2 independent experiments performed in technical triplicates. (D) SAH-RSVFBD prevented viral infection of A549 cells by RSV-A2, RSV 2-20, and RSV-rA2Line19F, as assessed by HEp-2 cell plaque assay and measurement of viral titers (pfu/ml). Data are mean ± SEM for 2 independent experiments performed in technical triplicates. *P < 0.001, **P < 0.0001.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts