NADH oxidase (Eimeria spp.) (NOX)

NADH oxidase (NOX) is a flavin-dependent enzyme found in Eimeria species, which are apicomplexan parasites responsible for coccidiosis in poultry and other livestock (Ni et al., 2019). The enzyme catalyzes the oxidation of NADH to NAD+ while reducing molecular oxygen to water or hydrogen peroxide, playing a pivotal role in maintaining the intracellular redox balance (Wang et al., 2021). In Eimeria, this activity is crucial for regenerating the NAD+ pool required for glycolysis, the parasite's primary energy source during its rapid replication phases. Because the parasite's survival is heavily dependent on this metabolic pathway, NOX is considered a high-priority therapeutic target for the development of new coccidiostats. Inhibition of NOX leads to a metabolic crisis characterized by the depletion of NAD+ and the cessation of ATP production, effectively halting the parasite's life cycle. Drugs such as robenidine have been shown to interfere with these energy-related pathways by inhibiting NADH oxidase activity, although the development of resistance remains a significant challenge in veterinary medicine (Fairlamb et al., 1977; PubChem, CID 25021). Targeting NOX offers a strategic approach to controlling infections that cause substantial economic damage to the global poultry industry.

Other names

NADH:oxygen oxidoreductaseEtNOXNicotinamide adenine dinucleotide oxidaseWater-forming NADH oxidase

Inhibition of the NADH oxidase enzyme prevents the regeneration of NAD+ from NADH, which is essential for maintaining glycolytic flux and energy production in the parasite, ultimately leading to its death.