In Vitro Anti-Parasitic Effects of Scorpion Peptides Smp24 and Smp43 on Trichinella spiralis: Toxicity, Ultrastructural Alterations, Molecular Docking, and Gene Expression.

“In Vitro Anti-Parasitic Effects of Scorpion Peptides Smp24 and Smp43 on Trichinella spiralis: Toxicity, Ultrastructural Alterations, Molecular Docking, and Gene Expression. Ibrahim HAM(1), Hussein AAA(2), Abdelmaksoud HF(3), Al-Awadhi RM(4), Elnahas SMM(1), Saleh AM(5), Megahed FAK(6), Abdel-Rahman MA(7), Ayed AS(8). Author information: (1)Zoology Department, Faculty of Science, Suez Canal University, Ismailia, 41522, Egypt. (2)Medical Malacology Department, Theodor Bilharz Research Institute, Giza, Egypt. (3)Parasitology Department, Theodor Bilharz Research Institute, Giza, Egypt. (4)Department of Science, College of Basic Education, The Public Authority for Applied Education and Training (PAAET), Kuwait. (5)Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt. (6)Nucleic Acid Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA City), 21934, Alexandria, Egypt. (7)Zoology Department, Faculty of Science, Suez Canal University, Ismailia, 41522, Egypt. Electronic address: mohamed_hassanain@science.suez.edu.eg. (8)Zoology Department, Faculty of Science, Suez Canal University, Ismailia, 41522, Egypt. Electronic address: aya_abdul-latif@science.suez.edu.eg. Trichinella spiralis is a zoonotic nematode responsible for trichinellosis, a disease with significant public health and economic implications. The current treatment of trichinellosis has limited efficacy, so the development of novel therapeutic agents is essential for effective parasite control. Scorpion venoms contain active compounds, including antimicrobial peptides (AMPs), which have efficacy against a variety of microbes principally through membrane destruction. In this study, the in vitro anti-parasitic effects of Smp24 and Smp43, scorpion venom-derived AMPs, were evaluated against T. spiralis through toxicity assays, ultrastructural analysis, molecular docking, and gene expression profiling. In vitro toxicity assays demonstrated significant inhibitory effects of Smp24 and Smp43 (0-100μg/mL) against adult worms and muscle larvae in a dose- dose-time dependent manner. Ultrastructural SEM analysis after treatment of either Smp24 or Smp43 at LC50 concentrations for 48 hours revealed extensive morphological and structural damage in treated parasites, including disruption of the cuticle, indicating a direct cytotoxic effect. Molecular docking studies predicted strong binding interactions between Smp24, Smp43, and T. spiralis thymidylate synthase, suggesting inhibition of DNA synthesis as a potential mechanism of action. Moreover, gene expression revealed significant upregulation in apoptosis-related genes (Casp3, Casp9, P53) and downregulation of oncogene marker (Ras) in both T. spiralis adult worms and muscle larvae after treatment with the LC50 of Smps peptides, indicating the induction of apoptosis. These findings highlight the potent antiparasitic activity of Smp24 and Smp43 through multiple mechanisms, including direct toxicity, thymidylate synthase inhibition, and apoptotic cell death, suggesting they are promising candidates for controlling T. spiralis infections. Copyright © 2026. Published by Elsevier Ltd. Conflict of interest statement: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.”