Biology subjects

Macleod, S.-L.

Publications and source records attributed to Macleod, S.-L..

3 recordsLinked to original sources

bioRxiv2026

Antiviral sugar baits to reduce arbovirus transmission: a proof-of-concept study

Dengue virus (DENV) and chikungunya virus (CHIKV) remain major global health threats, yet approved antiviral therapies are lacking. Antiviral sugar baits (AVSBs) represent a novel transmission-blocking strategy that exploits the natural sugar-feeding behaviour of mosquitoes to deliver antiviral compounds directly to the mosquito vector. In this study, we evaluated the antiviral efficacy of AVSBs containing JNJ-A07, {beta}-D-N4-hydroxycytidine (NHC), molnupiravir (MPV), and 4'-fluorouridine (4'FlU) in Aedes aegypti mosquitoes. An ex vivo mosquito gut model was used to select antiviral concentrations and to assess the ability of 4'FlU to reach the mosquito midgut following sugar feeding. AVSBs were subsequently evaluated for their effects on mosquito attractiveness, longevity, fecundity, and fertility, as well as their ability to suppress DENV and CHIKV infection in vivo. 4'FlU potently inhibited CHIKV replication in ex vivo mosquito guts and retained antiviral activity following sugar-bait administration. None of the antiviral compounds affected mosquito attraction to the bait, while only modest and compound-specific effects on mosquito fitness were observed. AVSBs containing JNJ-A07 significantly reduced DENV infection and dissemination, whereas 4'FlU-containing AVSBs significantly reduced CHIKV infection and viral loads. In contrast, NHC- and MPV-containing AVSBs did not exhibit antiviral activity in vivo. Collectively, these findings provide proof-of-concept for AVSBs as a novel strategy to reduce arbovirus transmission by targeting viral replication within the mosquito vector, suggesting that AVSBs could complement existing arbovirus control measures.

microbiology↗

bioRxiv2025

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

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.

microbiology↗

bioRxiv2024

Star-polymers as potent broad-spectrum extracellular virucidal antivirals

Viruses pose a significant threat to both global health and the global economy. It is clear that novel antiviral strategies are urgently needed, with a broad-spectrum approach being most desired. We have discovered a broad-spectrum, non-toxic polymer virucide that can tackle the viral threat. This polymeric virucide is effective at nanomolar concentrations, against a broad-spectrum of viruses and, demonstrated using an intranasal respiratory syncytial virus (RSV) murine model, has excellent efficacy, low anti-coagulant properties and low toxicity in vivo. Molecular dynamic simulations show that this polymer achieves its virucidal antiviral effect via self-assembly of viral-receptors leading to increased envelope forces and viral disassembly. The discovery of this cheap and readily produced polymer marks the start of a new type of receptor-crosslinking broad-spectrum antiviral that has significant potential to combat the global threat posed by viruses.

microbiology↗