Scorpion venom as a source of new antimicrobial agents

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  Scorpion venom as a source of new antimicrobial agents Abstract 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 format...

Sexual Dimorphism and Intraspecific Toxin Variation in Crotalus durissus terrificus Venom: Insights from Proteomics, Peptidomics, and Structural Modeling

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Sexual Dimorphism and Intraspecific Toxin Variation in Crotalus durissus terrificus Venom: Insights from Proteomics, Peptidomics, and Structural Modeling

The venom of the South American rattlesnake Crotalus durissus terrificus (Cdt) is renowned for its minimalist yet highly toxic arsenal. Intraspecific variability in expressed proteoforms and toxin content has been previously observed in Cdt venom, resulting in heterogeneous biological activities. In light of this, our study conducted an in-depth mass spectrometry-based analysis, combined with structural prediction to comprehensively assess Cdt venom variability and sexual dimorphism. Using peptidomic analysis, we identified 76 native peptides within Cdt venom, predominantly (63%) associated with noncanonical processing of crotoxin subunits, and 9 novel peptides via de novo sequencing. Quantitative analysis showed increased abundance of two crotapotin-derived peptides in females, while three novel peptides were significantly increased in males. Through quantitative proteomics, we characterized a repertoire of 33 proteins, with over one-third displaying sex-based differences in abundance. Furthermore, variant analysis revealed 12 novel toxin variants, generally at lower abundance than previously described proteoforms. Predictive three-dimensional structure modeling revealed conserved scaffolds, suggesting preservation of their biological activities. Addressing venom variability provides valuable insights into the intricate variability of Cdt venom, contributing to the understanding of its biological, medical, and biotechnological implications.

Jackson G. Miyamoto, Jackelinne Y. Hayashi, Giuseppe G. Figueirêdo Leite, Sávio S. Sant’Anna, Hang Fai Kwok, Richard H. Valente, Anita M. Tanaka-Azevedo, Alexandre K. Tashima; Sexual Dimorphism and Intraspecific Toxin Variation in Crotalus durissus terrificus Venom: Insights from Proteomics, Peptidomics, and Structural Modeling. J. Proteome Res. 2026; https://doi.org/10.1021/acs.jproteome.6c00275