Expanding the Antiviral Spectrum of Scorpion-Derived Peptides Against Toscana Virus and Schmallenberg Virus

Toscana virus (TOSV) and Schmallenberg virus (SBV) are arthropod-borne viruses from the <i>Bunyaviricetes</i> class, posing significant human and animal health threats. TOSV, endemic to the Mediterranean region, is a notable human pathogen detected in various animals, suggesting potential zoonotic reservoirs. SBV emerged in Europe in 2011, affecting ruminants and causing reproductive issues, with substantial economic implications. The rapid spread of both viruses underscores the need for novel antiviral strategies. Host defense peptides (HDPs), particularly those derived from scorpion venom, are gaining attention for their antiviral potential. This study investigated pantinin-1 and pantinin-2 for their inhibitory activity against TOSV and SBV by plaque reduction assay, tissue culture infective dose (TCID₅₀) determination, and the analysis of <i>M</i> gene expression via qPCR. Both peptides exhibited potent virucidal activity, with IC₅₀ values of approximately 10 µM, depending on the specific in vitro cell model used. Additionally, the selectivity index (SI) values were favorable across all virus/cell line combinations, with particularly optimal results observed for pantinin-2. In human U87-MG neuronal cells, both peptides effectively blocked TOSV infection, a critical finding given the virus's association with neurological conditions like encephalitis. The strong efficacy of these peptides against these viruses underscores the broader applicability of venom-derived peptides as promising antiviral agents, particularly in the context of emerging viral pathogens and increasing resistance to conventional therapeutics. Further studies are needed to optimize their antiviral potency and to assess their safety in vivo using animal models.