Targeting the Toxoplasma parasite sirtuin, TgSIR2A as a novel therapeutic strategy for Toxoplasmosis

Toxoplasmosis, caused by the parasite Toxoplasma gondii, affects nearly one-third of the global population. Current treatments have serious side effects and cannot eliminate the dormant cyst stage. This study focuses on TgSIR2A, a sirtuin protein involved in parasite survival and development. A 3D model of TgSIR2A was created, and ~2 million compounds were screened in silico. Promising candidates with strong binding and low predicted toxicity to human sirtuins were tested in vitro. Ligand 11 emerged as a potent and selective inhibitor, reducing parasite growth and showing strong therapeutic potential against T. gondii.