Identification of Mtb EthR Inhibitors

Identification of Mycobacterium tuberculosis transcriptional repressor EthR inhibitors

Tuberculosis (TB) has plagued humanity since prehistoric times, and the rise of drug-resistant strains has only made it harder to combat. Ethionamide (ETH), a second-line drug, targets mycolic acid synthesis in TB bacteria but requires activation by the EthR protein. Our research has focused on finding new ways to enhance this activation process. In an exciting development, we have identified three promising molecules that could serve as ETH boosters by inhibiting the EthR protein. Advanced techniques like molecular docking, molecular dynamics simulations, and binding free energy studies confirmed the potential of those identified compounds as effective EthR inhibitors. Additionally, machine learning methods evaluated their toxicity and synthesisability, confirming their safety and ease of synthesis. This breakthrough offers new hope in the battle against this ancient disease. Check out this published article “Identification of Mycobacterium Tuberculosis Transcriptional Repressor EthR Inhibitors: Shape-Based Search and Machine Learning Studies” in Heliyon.