A pan-respiratory virus attachment inhibitor with high potency in human airway models and in vivo

  1. Gregory Mathez
  2. Paulo Jacob Silva
  3. Vincent Carlen
  4. Charlotte Deloizy
  5. Clémentine Prompt
  6. Anaïs Hubart
  7. Joana Rocha-Pereira
  8. Marie Galloux
  9. Ronan Le Goffic
  10. Francesco Stellacci
  11. Valeria Cagno

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Abstract

Respiratory viruses can cause severe infections, often leading to hospitalization or death, and pose a major pandemic threat. No broad-spectrum antiviral is currently available. However, most respiratory viruses use sialic acid or heparan sulfates as attachment receptors. Here, we report the identification of a pan-respiratory antiviral strategy based on mimicking both glycans. We synthesized a modified cyclodextrin that simultaneously mimics heparan sulfate and sialic acid. This compound demonstrated broad-spectrum antiviral activity against important human pathogens: parainfluenza virus 3, respiratory syncytial virus, influenza virus H1N1, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, the compound is active against avian strains of influenza virus, revealing its importance for pandemic preparedness. The compound retains broad-spectrum activity in ex vivo models of respiratory tissues and in vivo against respiratory syncytial virus and influenza virus, using prophylactic and therapeutic strategies. These findings contribute to the development of future treatments and preventive measures for respiratory viral infections.

Article activity feed

  1. Version published to 10.1126/sciadv.adv9311
  2. Rapid Reviews Infectious Diseases

    Aartjan Velthuis

    Review 1: "A Pan-Respiratory Virus Attachment Inhibitor with High Potency in Human Airway Models and In Vivo"

    All reviewers commended the study for its innovative approach in developing a bifunctional β-cyclodextrin-based compound that mimics both sialic acid and heparan sulfate receptors, thereby demonstrating broad-spectrum antiviral activity.

  3. Rapid Reviews Infectious Diseases

    Barry O'Keefe

    Review 3: "A Pan-Respiratory Virus Attachment Inhibitor with High Potency in Human Airway Models and In Vivo"

    All reviewers commended the study for its innovative approach in developing a bifunctional β-cyclodextrin-based compound that mimics both sialic acid and heparan sulfate receptors, thereby demonstrating broad-spectrum antiviral activity.

  5. Version published to 10.1101/2025.01.25.634704 on bioRxiv