Nitazoxanide Inhibits the Bifunctional Enzyme GlG6PD::6PGL of Giardia lamblia: Biochemical and In Silico Characterization of a New Druggable Target

Giardiasis, which is caused by Giardia lamblia infection, a relevant cause of morbidity and mortality worldwide. Because no vaccines are currently available to treat giardiasis, chemotherapeutic drugs the main options for controlling infection. Evidence has shown that nitro drug nitazoxanide (NTZ) commonly prescribed treatment giardiasis; however, mechanisms underlying NTZ’s antigiardial activity not well-understood. Herein, we identified glucose-6-phosphate::6-phosphogluconate dehydrogenase (GlG6PD::6PGL) fused enzyme as target, NTZ behaves GlG6PD::6PGL catalytic inhibitor. Furthermore, fluorescence assays suggest alterations in stability protein, whereas results indicate loss due conformational folding changes. Molecular docking dynamic simulation studies model binding on active site G6PD domain near structural NADP+ site. The findings this study provide novel mechanistic basis strategy drug.