Wasp venom peptide as a new antichagasic agent

Area of Science:

• Parasitology and Tropical Diseases
• Drug Discovery and Development
• Biochemistry and Molecular Biology

Background:

• Chagas disease, caused by *Trypanosoma cruzi*, affects millions globally, with limited, toxic treatment options.
• Existing drugs like benznidazole and nifurtimox exhibit low efficacy and high toxicity.
• Antimicrobial peptides (AMPs) are emerging as potential therapeutic agents against various pathogens.

Purpose of the Study:

• To evaluate the antichagasic efficacy of polybia-CP, an AMP from *Polybia paulista* wasp venom.
• To investigate the mechanism of action of polybia-CP against different *T. cruzi* life cycle stages.
• To assess the selectivity of polybia-CP against mammalian cells.

Main Methods:

• Testing polybia-CP against epimastigote, trypomastigote, and amastigote forms of a benznidazole-resistant *T. cruzi* strain.
• Assessing peptide selectivity using LLC-MK2 mammalian cells.
• Investigating the mechanism of action via flow cytometry, SEM, and enzymatic assays targeting *T. cruzi* GAPDH.

Main Results:

• Polybia-CP inhibited the development of all tested *T. cruzi* forms.
• The peptide demonstrated high selectivity for trypanosomal cells over mammalian cells (selectivity index >106).
• Mechanism involves phosphatidylserine exposure, increased reactive oxygen species (ROS), reduced mitochondrial potential, and cell shrinkage, indicating apoptosis.

Conclusions:

• Polybia-CP exhibits potent antichagasic activity against various *T. cruzi* stages, including drug-resistant strains.
• The peptide induces trypanocidal effects through apoptotic cell death pathways.
• Polybia-CP represents a promising lead compound for developing novel, selective anti-Chagas disease therapeutics.