CARACTERÍSTICAS DO ENVENENAMENTO DOS PRINCIPAIS ANIMAIS PEÇONHENTOS DO ESTADO DE MATO GROSSO DO SUL E ESTUDOS in silico DAS TOXINAS

Abstract

Toxinology is essential for the bioprospecting of new pharmaceuticals derived from the study of venoms and toxins. The rise of antimicrobial resistance poses a growing and essential challenge to public health, making antimicrobial peptides (AMPs) a promising therapeutic alternative. A literature review examined the main aspects of bee, scorpion, and snake envenomation of medical interest in Brazil, with a view to understanding their implications. This study evaluated and optimized the potential of AMPs derived from animal toxins (TsAP-1, BatxC, and Melittin) for the development of new antibiotic agents. The native peptide three-dimensional structures were determined using AlphaFold modeling and validated with PROCHECK. Following confirmation of interaction with bacterial DNA gyrase, peptide mutations were introduced to increase the net positive charge and amphipathicity. The silico predictive data demonstrate the efficacy of the optimization: the TsAP-1 peptide had its activity increased from 30% to 98%, and BatxC reached 99%; the mutant Melittin maintained its immense efficacy. Although Melittin-M maintains the maximum predicted activity of 99%, structural analysis highlights the high hemolytic activity inherent to its mechanism of action. This factor imposes a critical limitation on its applicability. The integrated computational approach validates the optimization of physicochemical and structural properties to improve stability and membrane affinity. However, a complete evaluation of the therapeutic potential requires rigorous in vitro experimental validation of the mutant peptides, including determination of the spectrum of action against both Gram-positive and Gram-negative strains and strict cytotoxicity assays, to ensure the safety and clinical viability of the optimized compounds.