Scorpion Peptides in Antiviral Drug Discovery: An In-depth Review.

Despite remarkable progress in the fields of vaccinology and antiviral therapy, viral infections persist as a leading cause of morbidity and mortality worldwide. Therefore, it is crucial to identify new and effective antiviral drug candidates. Scorpion venoms are viewed as a rich source of structurally diverse and biologically active peptides, which may present opportunities for diagnostic, preventive, and therapeutic applications. This review intends to provide a contemporary and detailed analysis of scorpion-derived peptides, with a particular focus on their structural diversity, cytotoxic effects, antiviral properties, and mechanisms of action. Additionally, this paper highlights several potential fruitful areas for future studies. Current evidence indicates that scorpion-derived peptides are effective against a wide array of medically important viral pathogens such as chikungunya virus, dengue virus, enterovirus 71, hepatitis B virus (HBV), herpes simplex virus 1, human immunodeficiency virus 1, influenza A virus (IAV), severe acute respiratory syndrome coronavirus-2, and Zika virus. Nevertheless, the majority of these findings have been obtained from in vitro studies, whereas evidence from animal models remains limited and clinical evaluation in humans is currently unavailable. Available studies suggest that these peptides may act through diverse mechanisms of action, including direct virucidal activity, inhibition of viral entry, immune system modulation, reduction of virus-induced cytopathic effects, and suppression of viral gene expression. Emerging evidence also demonstrates the efficacy of certain scorpion-derived peptides in animal models of HBV, IAV, and Newcastle disease virus infection. Overall, such peptides appear to inaugurate new avenues for the treatment of viral infections.