Anti-Toxoplasma gondii studies of the venom peptide XYP4 from the Lycosa coelestis.

Toxoplasma gondii (T. gondii) is an intracellular parasite with multiple routes of infection that poses a serious health risk to pregnant women, fetuses, and immunocompromised populations. Currently, clinical drugs in the treatment of toxoplasmosis continue to face challenges such as drug resistance. In the face of this challenge, researchers have gradually focused on the potential medicinal value of animal venoms in the fight against T. gondii, especially venom peptides showing advantages such as high potency, membrane targeting, and immunomodulation. The present study aimed to explore whether XYP4, a peptide derived from the venom of the Lycosa coelestis (L. coelestis), possesses better anti-T. gondii activity and its mode of action. The experimental results showed that XYP4 is an amphiphilic cationic linear polypeptide with an α-helix, which can exert anti-toxoplasma activity at low concentrations, affecting the lytic cycle. This polypeptide showed moderate survival benefits in mice infected with T. gondii. The main modes of action of XYP4 include inhibition of tachyzoites' intracellular proliferation, modulation of inflammatory factor expression in the host cells, and disruption of tachyzoite membrane integrity.