Mathez Gregory, Silva Paulo Jacob, Carlen Vincent, Deloizy Charlotte, Prompt Clémentine, Hubart Anaïs, Rocha-Pereira Joana, Galloux Marie, Le Goffic Ronan, Stellacci Francesco, Cagno Valeria
Institute of Microbiology, University Hospital of Lausanne, University of Lausanne, 1011 Lausanne, Switzerland.
Institute of Materials, École Polytechnique Fédérale de Lausanne, 1015 Lausanne , Switzerland.
Sci Adv. 2025 Aug;11(31):eadv9311. doi: 10.1126/sciadv.adv9311. Epub 2025 Aug 1.
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.
呼吸道病毒可引发严重感染，常常导致住院或死亡，并构成重大的大流行威胁。目前尚无广谱抗病毒药物。然而，大多数呼吸道病毒利用唾液酸或硫酸乙酰肝素作为附着受体。在此，我们报告了一种基于模拟这两种聚糖的泛呼吸道抗病毒策略。我们合成了一种同时模拟硫酸乙酰肝素和唾液酸的修饰环糊精。该化合物对重要的人类病原体显示出广谱抗病毒活性：副流感病毒3型、呼吸道合胞病毒、甲型流感病毒H1N1以及严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。此外，该化合物对禽流感病毒株也有活性，显示出其在大流行防范方面的重要性。使用预防和治疗策略时，该化合物在呼吸道组织的体外模型以及体内对呼吸道合胞病毒和流感病毒均保持广谱活性。这些发现有助于未来呼吸道病毒感染治疗方法和预防措施的开发。
