Evaluation of Human-Approved Active Pharmaceutical Ingredients Against Lactate Dehydrogenase from Theileria annulata

BackgroundTheileriosis, a tick-borne disease caused by Theileria annulata, leads to global economic losses in livestock, emphasizing an urgent need for the identification of new therapeutic agents with alternative mechanisms of action due to rising buparvaquone resistance combined with climate-driven spread. T. annulata lactate dehydrogenase (TaLDH) has been selected as a promising target in the current study. As approximately half of the FDA-approved veterinary drugs are shared with human medicine, integrating drug repurposing has gained importance as an emerging strategy for the management of tick-borne diseases. MethodsIn this study, in vitro and in silico approaches are integrated to screen 21 Active Pharmaceutical Ingredients (APIs) from FDA-approved drugs against TaLDH in the context of drug repurposing. Results Six of 21 the APIs showed ≥ 60% inhibition against TaLDH (over 95% purity), particularly the proton pump inhibitor omeprazole, which exhibited both the highest inhibition percentage (73.36%) and the lowest binding energy (- 6.36 kcal/mol), with a consistency between experimental and computational results. To our knowledge, this study is the first to evaluate FDA-approved human therapeutics as potential TaLDH inhibitors. Conclusion This preliminary in vitro enzymatic inhibition study suggests omeprazole as a potential therapeutic agent for theileriosis. However, comprehensive pharmacokinetic and pharmacodynamic analyses will further validate and advance these promising findings. Furthermore, APIs with ≥ 60% inhibition of TaLDH may serve as promising leads for the future development of more potent anti-theilerial agents through targeted derivatization and lead optimization. In alignment with the One Health framework, evaluating human-approved active pharmaceutical ingredients as veterinary therapeutic against parasitic diseases may offer a sustainable, time and cost-efficient strategy.