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

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.