Advances in computational design have greatly accelerated antimicrobial peptide engineering. In this study, three Plasmodium chabaudi-derived peptides (PcDBS1R1, PcDBS1R5, and PcDBS1R9), generated using the Joker computational design algorithm, were synthesized and characterized for their structural and functional properties. Biophysical analyses revealed that PcDBS1R5 and PcDBS1R9 predominantly adopted α-helical structures with high amphipathicity, whereas PcDBS1R1 exhibited greater structural plasticity. PcDBS1R5 and PcDBS1R9 displayed antibacterial activity against an Acinetobacter baumannii clinical isolate, whereas PcDBS1R1 showed pronounced antibiofilm effects. None of the peptides exhibited cytotoxicity toward murine macrophages, and all significantly reduced nitric oxide production in lipopolysaccharide-stimulated macrophages, suggesting potential anti-inflammatory activity. Overall, these findings demonstrate that computer-aided design of P. chabaudi-derived peptides can yield molecules with antibiofilm, and immunomodulatory properties, minimal cytotoxicity, and promising therapeutic potential as scaffolds for next-generation peptide-based treatments targeting biofilm-associated bacterial infections.
Orozco et al. (2026) studied this question.