Malaria continues to pose a worldwide health concern, with the emergence of drug resistance requiring novel treatments. The development of pharmaceuticals is expensive and protracted, particularly for tropical diseases that yield minimal economic benefits.

Our research centers on Plasmodium falciparum CK2α (pfCK2α), a crucial parasite kinase that exhibits similarity with human CK2α, a target for current anticancer pharmaceuticals. We elucidated the structure of a human CK2α inhibitor complexed with pfCK2α by X-ray crystallography. Structural study indicated that pfCK2α demonstrates significant resemblance to its human equivalent at the active site, with considerable variations in adjacent regions. The anticancer drug inhibits human CK2α by attaching to its ATP-binding pocket and operates similarly in pfCK2α. The inhibitor proficiently occupies the ATP-binding site of pfCK2α, impeding its catalytic function.

Our findings offer structural evidence endorsing the repurposing of human CK2α-targeting anticancer agents as antimalarial therapies. The recognized structural variations also provide a basis for the development of malaria-specific CK2α inhibitors. The distinctive characteristics of pfCK2α present chances to improve selectivity and diminish negative effects in future medication optimization. This method meets the urgent demand for novel antimalarial medicines while establishing a framework for systematic drug creation relevant to other parasitic illnesses with conserved kinase targets.