High-Throughput\nSynthesis and Evaluation of Antiviral\nCopolymers for Enveloped Respiratory Viruses

COVID-19\nmade apparent the devastating impact viral pandemics\nhave\nhad on global health and order. Development of broad-spectrum antivirals\nto provide early protection upon the inevitable emergence of new viral\npandemics is critical. In this work, antiviral polymers are discovered\nusing a combination of high-throughput polymer synthesis and antiviral\nscreening, enabling diverse polymer compositions to be explored. Amphipathic\npolymers, with ionizable tertiary amine groups, are the most potent\nantivirals, effective against influenza virus and SARS-CoV-2, with\nminimal cytotoxicity. It is hypothesized that these polymers interact\nwith the viral membrane as they showed no activity against a nonenveloped\nvirus (rhinovirus). The switchable chemistry of the polymers during\nendosomal acidification was evaluated using lipid monolayers, indicating\nthat a complex synergy between hydrophobicity and ionization drives\npolymer–membrane interactions. This new high-throughput methodology\ncan be adapted to continue to engineer the potency of the lead candidates\nor develop antiviral polymers against other emerging viral classes.