The potential of classical antibacterial peptides in mammalian antiviral chemotherapy

Classical antimicrobial peptides (AMPs) were historically isolated from natural sources and selected based on their ability to kill bacteria in vitro. With viral infections being increasingly recognized as a major health-care threat, especially after the COVID-19 pandemic, a label extension was attempted to use AMPs as anti-viral agents. This hypothesis is based on the various modes of action of AMPs, including membrane disintegration (for enveloped viruses), direct protein or nucleic acid targets or host defense functions. Although some of the classical AMPs indeed have deleterious effects on viral assembly and propagation, their in vitro activity levels (20–50 µg mL–1) against viruses are inferior to their anti-bacterial properties. Even when some anti-viral activity is found, the mode of action speculations seem to be more guesses than conclusions from well-controlled assays. Very few AMPs were tested for anti-viral efficacy in mammals, and the results are less than encouraging for clinical development. Peptide therapeutics designed or identified directly for virology research appear to be superior to AMPs label extensions.