Inhibitory effect of morin on aldolase 2 from Eimeria tenella. (December 2022) - Hu, Junjing
Abstract: Eimeria tenella ( E. tenella ) is a protozoal parasite that can cause severe cecal lesions and death in chickens, seriously harming the chicken industry. Conventional control strategies mainly rely on anticoccidial drugs. However, the emerging problems of anticoccidial resistance and drug residues necessitate exploring potential drug targets for developing new anticoccidial drugs. Fructose-1, 6-bisphosphate aldolase (ALD) is an essential enzyme for parasite energy metabolism that has been considered a potential drug target. In this study, we analyzed the molecular and biochemical properties of E. tenella ALD2 ( Et ALD2). Et ALD2 mRNA expression was highest in second-generation merozoites, whereas the protein level was highest in unsporulated oocysts. Indirect immunofluorescence showed that Et ALD2 was mainly distributed in sporozoite' cytoplasm. The natural product inhibitor (morin) was screened by computer-aided drug screening. Enzyme kinetic and inhibition kinetic assays showed that morin had a good inhibitory effect on Et ALD2 activity (IC50 = 10.37 μM, Ki = 48.97 μM). In vitro inhibition assay demonstrated that morin had an inhibitory effect on E. tenella development, with an IC50 value of 3.98 μM and drug selection index of 177.49. In vivo, morin significantly improved cecal lesions ( p < 0.05) and reduced oocyst excretion ( p < 0.05) in E. tenella -infected chickens compared with the untreated group. The anticoccidial index of the group receiving 450 mg morin per kg feed was 162, showing a good anticoccidial effect. These findings suggest that Et ALD2 could be a novel drug target for E. tenella treatment, and morin should be further evaluated as a therapeutic candidate for chicken coccidiosis. Graphical abstract: Image 1 Highlights: The molecular and biochemical properties of Eimeria tenella aldolase 2 ( Et ALD2) was investigated for the first time. Morin had inhibitory effect on Et ALD2 activity and E. tenella development. Morin improved cecal lesions and reduced oocyst excretion, showing a good anticoccidial effect.