Virucidal activity of a scorpion venom peptide variant mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses

► We investigated the antiviral activities of mucroporin and optimized mucroporin-M1. ► Mucroporin and mucroporin-M1 were scorpion venom-derived host defense peptides. ► Mucroporin-M1 but not mucroporin had antiviral activities against tested viruses. ► The tested viruses were measles, SARS-CoV and influenza H5N1 viruses. ► Mucroporin-M1 exerted its effects on viruses by directly binding to virus membranes. Outbreaks of SARS-CoV, influenza A (H5N1, H1N1) and measles viruses in recent years have raised serious concerns about the measures available to control emerging and re-emerging infectious viral diseases. Effective antiviral agents are lacking that specifically target RNA viruses such as measles, SARS-CoV and influenza H5N1 viruses, and available vaccinations have demonstrated variable efficacy. Therefore, the development of novel antiviral agents is needed to close the vaccination gap and silence outbreaks. We previously indentified mucroporin, a cationic host defense peptide from scorpion venom, which can effectively inhibit standard bacteria. The optimized mucroporin-M1 can inhibit gram-positive bacteria at low concentrations and antibiotic-resistant pathogens. In this investigation, we further tested mucroporin and the optimized mucroporin-M1 for their antiviral activity. Surprisingly, we found that the antiviral activities of mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses were notably increased with an EC50 of 7.15μg/ml (3.52μM) and a CC50 of 70.46μg/ml (34.70μM) against measles virus, an EC50 of 14.46μg/ml (7.12μM) against SARS-CoV and an EC50 of 2.10μg/ml (1.03μM) against H5N1, while the original peptide mucroporin showed no antiviral activity against any of these three viruses. The inhibition model could be via a direct interaction with the virus envelope, thereby decreasing the infectivity of virus. This report provides evidence that host defense peptides from scorpion venom can be modified for antiviral activity by rational design and represents a practical approach for developing broad-spectrum antiviral agents, especially against RNA viruses.