The University of Illinois, Chicago is conducting a $800,624 Project Grant awarded by the National Institute of Allergy and Infectious Diseases (CFDA 93.855 Allergy and Infectious Diseases Research) to develop novel thioredoxin glutathione reductase (TGR) inhibitors for the treatment of schistosomiasis. The project aims to optimize TGR inhibitors using computational design, medicinal chemistry, and structural biology to improve potency, selectivity, and pharmacological properties. A sub-award of $155,000 to Rush University Medical Center will assess the inhibitor compounds for efficacy against schistosome parasites and mammalian cell toxicity. Another sub-award of $280,000 to the University of L'Aquila in Italy will determine the crystal structures and binding modes of the inhibitor compounds to TGR using X-ray crystallography and cryo-electron microscopy. The overall goal is to identify novel TGR inhibitors with the potential to treat schistosomiasis, a neglected tropical disease that affects hundreds of millions globally.