Antiviral peptide engineering for targeting membrane-enveloped viruses: Recent progress and future directions

Membrane-enveloped viruses are a major cause of global health challenges, including recent epidemics and pandemics. This mini-review covers the latest efforts to develop membrane-targeting antiviral peptides that inhibit enveloped viruses by 1) preventing virus-cell fusion or 2) disrupting the viral membrane envelope. The corresponding mechanisms of antiviral activity are discussed along with peptide engineering strategies to modulate membrane-peptide interactions in terms of potency and selectivity. Application examples are presented demonstrating how membrane-targeting antiviral peptides are useful therapeutics and prophylactics in animal models, while a stronger emphasis on biophysical concepts is proposed to refine mechanistic understanding and support potential clinical translation.