Exploring MurE Protein Inhibitors of Tropheryma Whipplei Through Pharmacoinformatic Approaches Incorporating Solubility-Enhancing Formulation Insights

The study investigates potential drug targets for Tropheryma whipplei, the bacterium responsible for Whipple disease, which is resistant to fluoroquinolones and cannot be cultured in axenic media. The enzyme murE was identified as a promising drug target. Over 1,000 Ayurvedic compounds were screened, and three candidates—Ergost-5-en-3-ol (3beta,24xi), [6]-Gingerdiol 3-monoacetate, and Valtrate—showed strong binding to the target enzyme. Molecular dynamics simulations confirmed stable interactions, and ADMET analysis revealed low water solubility, which was improved with cyclodextrin SBE-β-CD. None of the compounds were hepatotoxic, though Valtrate showed AMES toxicity. The study suggests further research on [6]-Gingerdiol 3-monoacetate to combat T. whipplei infections and overcome antibiotic resistance challenges.