High-Throughput Synthesis and Evaluation of Antiviral Copolymers for Enveloped Respiratory Viruses.

Autor: Mengist HM; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane 4072, Australia., Denman P; Centre for Materials Science, Queensland University of Technology, Brisbane 4000, Australia.; School of Chemistry and Physics, Queensland University of Technology, Brisbane 4000, Australia., Frost C; Centre for Materials Science, Queensland University of Technology, Brisbane 4000, Australia.; School of Chemistry and Physics, Queensland University of Technology, Brisbane 4000, Australia., Sng JDJ; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane 4072, Australia., Logan S; Centre for Materials Science, Queensland University of Technology, Brisbane 4000, Australia.; School of Chemistry and Physics, Queensland University of Technology, Brisbane 4000, Australia., Yarlagadda T; Centre for Immunology and Infection Control, Faculty of Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane 4000, Australia., Spann KM; Centre for Immunology and Infection Control, Faculty of Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane 4000, Australia., Barner L; School of Chemistry and Physics, Queensland University of Technology, Brisbane 4000, Australia., Fairfull-Smith KE; Centre for Materials Science, Queensland University of Technology, Brisbane 4000, Australia.; School of Chemistry and Physics, Queensland University of Technology, Brisbane 4000, Australia., Short KR; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane 4072, Australia., Boase NR; Centre for Materials Science, Queensland University of Technology, Brisbane 4000, Australia.; School of Chemistry and Physics, Queensland University of Technology, Brisbane 4000, Australia.
Jazyk: angličtina
Zdroj: Biomacromolecules [Biomacromolecules] 2024 Nov 11; Vol. 25 (11), pp. 7377-7391. Date of Electronic Publication: 2024 Oct 05.
DOI: 10.1021/acs.biomac.4c01049
Abstrakt: COVID-19 made apparent the devastating impact viral pandemics have had on global health and order. Development of broad-spectrum antivirals to provide early protection upon the inevitable emergence of new viral pandemics is critical. In this work, antiviral polymers are discovered using a combination of high-throughput polymer synthesis and antiviral screening, enabling diverse polymer compositions to be explored. Amphipathic polymers, with ionizable tertiary amine groups, are the most potent antivirals, effective against influenza virus and SARS-CoV-2, with minimal cytotoxicity. It is hypothesized that these polymers interact with the viral membrane as they showed no activity against a nonenveloped virus (rhinovirus). The switchable chemistry of the polymers during endosomal acidification was evaluated using lipid monolayers, indicating that a complex synergy between hydrophobicity and ionization drives polymer-membrane interactions. This new high-throughput methodology can be adapted to continue to engineer the potency of the lead candidates or develop antiviral polymers against other emerging viral classes.
Databáze: MEDLINE
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