Scorpion venom as a source of new antimicrobial agents

The escalating global threat of antimicrobial resistance necessitates urgent discovery of novel therapeutic agents. Scorpion venom, a complex cocktail of bioactive molecules, has emerged as a promising reservoir of antimicrobial peptides (AMPs) with potent activity against multidrug-resistant pathogens. This review comprehensively examines the structural and functional diversity of scorpion-derived AMPs and their therapeutic potential. Scorpion venom AMPs exhibit remarkable structural heterogeneity. Their physicochemical properties, characterized by cationic charge, amphipathicity, and α-helical or β-sheet conformations, underpin their antimicrobial efficacy. These peptides demonstrate broad-spectrum antimicrobial activity encompassing Gram-positive and Gram-negative bacteria, fungi, viruses, and parasites. Mechanistically, scorpion AMPs employ multifaceted strategies including membrane disruption through pore formation or carpet-like mechanisms, cell wall synthesis inhibition, intracellular interference with DNA replication and protein synthesis, biofilm dispersion, immunomodulation, and ion channel modulation. This polypharmacological approach has been proposed to lower the risk for resistance development relative to conventional antibiotics, though this remains to be comprehensively validated across diverse scorpion AMPs. Despite their therapeutic promise, challenges persist regarding cytotoxicity, proteolytic instability, and high production costs. However, rational engineering strategies, including sequence truncation, D-amino acid substitution, cyclization, and hybrid peptide design, are advancing clinical viability. Notable candidates have demonstrated exceptional potency in preclinical models. This review synthesizes current knowledge on scorpion venom AMPs, highlighting their advantages over traditional antibiotics and outlining optimization strategies. Future research directions emphasize structure-activity relationship studies, novel delivery systems, and comprehensive toxicological profiling. Scorpion venom represents an underexploited natural resource that may yield next-generation antimicrobial therapeutics critical for combating the growing threat of drug-resistant infections.