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

Respiratory viruses can cause severe infections, including bronchiolitis and pneumonia, often leading to hospitalization or death. Due to their ease of transmission, they are also scrutinized for their pandemic potential. 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 and characterized a unique modified cyclodextrin that simultaneously mimics heparan sulfate and sialic acid. This novel compound demonstrated broad-spectrum antiviral activity against important human pathogens: parainfluenza virus 3, respiratory syncytial virus, influenza virus H1N1, SARS-CoV-2. Additionally, the compound is active against different 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 experiments against RSV and Influenza virus, using both prophylactic and therapeutic strategies. These findings represent a significant step forward in the development of future treatments and preventive measures for respiratory viral infections.