Morin resists Cryptosporidium parvum infection by targeting the parasite fructose bisphosphate aldolase

Cryptosporidium parvum is a zoonotic intestinal pathogen that causes severe diarrheal disease in children and immunocompromised individuals, yet treatment options remain extremely limited. In this study, we identified fructose-1,6-bisphosphate aldolase (CpFBA) as a conserved and essential glycolytic enzyme in C. parvum, playing critical roles in energy metabolism, invasion, and proliferation. Using molecular docking, enzyme kinetics, and in vitro functional assays, we demonstrated that the natural flavonoid morin directly binds to and inhibits CpFBA activity, thereby impairing parasite glucose uptake, ATP production, and infectivity. More importantly, oral administration of morin in a suckling mouse model of cryptosporidiosis significantly reduced fecal oocyst shedding, alleviated intestinal pathology, and preserved epithelial barrier integrity.