Self-Assembled peptide nanofiber-based nanopharmaceutics for the treatment of viral infections

Rapid viral mutations make existing antiviral drugs ineffective, as seen during the SARS-CoV-2 pandemic, highlighting the need for therapeutic strategies that can adapt quickly. In this study, we developed a multi-targeted peptide nanofiber (PNF) system consisting of counterionic peptide amphiphiles (PAs) with distinct inhibitory actions. Negatively charged PAs incorporated heparin-inspired peptide sequence, designed based on heparin's known inhibitory features, along with various spacer sequences to evaluate their effectiveness against different SARS-CoV-2 variants. Positively charged PAs, enabling the formation of nanofibers, were selected from previously investigated inhibitory sequences. These PNF systems exhibited high inhibitory activity against both wild-type and mutant viruses, with variations in effectiveness, showcasing the adaptable nature of the system. Furthermore, nafamostat (NFM), a serine protease inhibitor, was encapsulated within the PNFs, which serve not only as structural components but also as cargo delivery agents. NFM enhanced overall treatment efficacy by enabling greater inhibition with lower PNF amounts.