Synthetic heparan sulfate mimics based on chitosan derivatives show broad-spectrum antiviral activity
Enveloped viruses enter cells by binding to receptors present on host cell membranes, which trigger internalization and membrane fusion. For many viruses, this either directly or indirectly involves interaction with membrane-anchored carbohydrates, such as heparan sulfate, providing a potential target for a broad-spectrum antiviral approach. Based on this hypothesis, we screened a library of functionalized chitosan sulfates that mimic heparan sulfate in cellular membranes for inhibition of SARS-CoV-2 and respiratory syncytial virus (RSV) entry. An array of compounds blocking SARS-CoV-2 and RSV were identified, with the lead compound displaying broad-spectrum activity against multiple viral strains and clinical isolates. Mechanism of action studies showed the drug to block viral entry irreversibly, likely via a virucidal mechanism. Importantly, the drug was non-toxic in vivo and showed potent post-exposure therapeutic activity against both SARS-CoV-2 and RSV. Together, these results highlight the potential of functionalized carbohydrates as broad-spectrum antivirals targeting respiratory viruses.
Authors
- Julia Revuelta (ORCID: https://orcid.org/0000-0001-6225-7336)
- María Gómez Martínez (ORCID: https://orcid.org/0009-0002-3261-4827)
- Santiago Ramón‐Maiques (ORCID: https://orcid.org/0000-0001-9674-8088)
- Jerónimo Bravo (ORCID: https://orcid.org/0000-0001-6695-2846)
- Francisco del Caño‐Ochoa (ORCID: https://orcid.org/0000-0003-3093-3103)
- Ana-Belén Blázquez (ORCID: https://orcid.org/0000-0002-0847-0977)
- Maria Lopez-Redondo (ORCID: https://orcid.org/0000-0002-3328-6821)
- Clara Francés‐Gómez (ORCID: https://orcid.org/0000-0001-7341-3824)
- Óscar Moreno (ORCID: https://orcid.org/0000-0002-8975-1411)
- Ana Isabel Avilés‐Alía (ORCID: https://orcid.org/0000-0003-0564-8984)
- Jordi Llop (ORCID: https://orcid.org/0000-0002-0821-9838)
- Anmol Adhav (ORCID: https://orcid.org/0000-0002-3504-8675)
- Alicia Forcada‐Nadal (ORCID: https://orcid.org/0000-0003-0179-4044)
- J.L. Llacer (ORCID: https://orcid.org/0000-0001-5304-1795)
- Miguel A. Martín-Acebes (ORCID: https://orcid.org/0000-0001-6015-3613)
- Nadine Gougeard (ORCID: https://orcid.org/0000-0001-7338-7267)
- Alfonso Fernández‐Mayoralas (ORCID: https://orcid.org/0000-0002-1241-7538)
- Roberto Gozalbo‐Rovira (ORCID: https://orcid.org/0000-0003-3427-3800)
- Alberto Marina (ORCID: https://orcid.org/0000-0002-1334-5273)
- Vicente Rubio (ORCID: https://orcid.org/0000-0001-8124-1196)
- Luciana Rusu (ORCID: https://orcid.org/0000-0002-2481-4047)
- Susana Iglesias
- Alfonso Gutiérrez‐Adán (ORCID: https://orcid.org/0000-0001-9893-9179)
- Ron Geller (ORCID: https://orcid.org/0000-0002-7612-4611)
- Clara Marco‐Marín (ORCID: https://orcid.org/0000-0002-8813-3515)
- María del Pilar Hernández-Sierra (ORCID: https://orcid.org/0009-0004-5618-0159)
- Acsah Konuparamban
- Elena Trapero
- Carolina Espinosa (ORCID: https://orcid.org/0009-0005-7504-3835)
- Eva Calvo Pinilla
Institutions
- Consejo Superior de Investigaciones Científicas (ES)
- Universitat de València (ES)
- Novo Nordisk Foundation (DK)
- CIC biomaGUNE (ES)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Centro de Investigación Biomédica en Red (ES)
- Instituto de Biomedicina de Valencia (ES)
- Institute for Integrative Systems Biology (ES)
- Instituto de Química Orgánica General (ES)
- Centro de Investigación en Sanidad Animal
Publication Details
- Journal
- Communications Biology
- Published
- 2025-03-04
- DOI
- https://doi.org/10.1038/s42003-025-07763-z
- Citations
- 9
- Primary Topic
- Proteoglycans and glycosaminoglycans research
- Type
- article
- Field-Weighted Citation Impact
- 10.36
Funders
- Ministerio de Ciencia, Innovación y Universidades
- European Commission
- Abdus Salam International Centre for Theoretical Physics
- Generalitat Valenciana
- HORIZON EUROPE Framework Programme