Repurposing Disease-Associated Inhibitors to Disrupt Thioredoxin Reductase in Cryptosporidium parvum

Cryptosporidiosis is a severe diarrheal disease caused by the protozoan parasite Cryptosporidium, posing a significant health risk to immunocompromised individuals and young children in low-resource settings. Current treatment options are limited, underscoring the urgent need for novel therapeutics. This project investigates thioredoxin reductase (CpTrxR), an essential enzyme in Cryptosporidium's redox homeostasis, as a potential drug target. We evaluated a panel of 20 inhibitors, previously shown to exhibit activity against diseases such as malaria, schistosomiasis, and cancer, for their efficacy against CpTrxR. Using a combination of biochemical assays, computational modeling, and structural analysis, we assessed each inhibitor’s potency and binding characteristics. While several compounds demonstrated measurable inhibition of CpTrxR, their IC₅₀ values were not sufficiently low to suggest strong potential as therapeutic candidates.