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bioRxiv · 10.1101/2025.10.27.684922

A broad-spectrum, biocompatible, virucidal polymer reduces chikungunya virus in murine models

Macleod, S.-L.·Loo, A. X. Y.·Castillo, M.·Batt, L. J.·Lum, F.-M.·Torres-Ruesta, A.·Ng, L. F. P.·Jones, S. T.
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Abstract

Autochthonous transmission of arboviruses poses significant threats to global health and economies. Yet, no effective antivirals exist. Building on our previous antiviral star-polymer, we designed zwitterionic star-polymers for efficacy in high protein environments. A polymer with 12% positively charged monomer (Zwitterionic Polymer-ZP12) exhibited broad-spectrum, biocompatible antiviral activity against Alphaviridae, Flaviviridae, Herpesviridae, and Picornaviridae. Using murine models for Chikungunya virus (CHIKV) infection, ZP12 treatment (10 mg/kg every 24 hours for 7 days) reduced tissue viral load by 90% 3 days post-infection and significantly alleviated CHIKV-induced joint swelling. Mechanistically, ZP12 downregulated CHIKV-driven immunopathogenesis by reducing viral load and dampening CD4+ T cell and macrophage activation in virus-infected joints. With no current antiviral interventions for these arboviruses, ZP12 represents a promising intervention for combating future pandemics.

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Macleod, S.-L., Loo, A. X. Y., Castillo, M., Batt, L. J., Lum, F.-M., Torres-Ruesta, A., Ng, L. F. P., Jones, S. T.. 2025-10-27. A broad-spectrum, biocompatible, virucidal polymer reduces chikungunya virus in murine models. https://doi.org/10.1101/2025.10.27.684922

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