A Computer-Aided Drug Repurposing: The Antibacterial Agents Targeting GroEL

This study presents a novel computational workflow for drug repurposing, focusing on identifying antibacterial agents targeting the bacterial chaperone GroEL. The workflow involves target screening, drug screening, and in vitro antibacterial experiments. It successfully identified daprodustat and ezetimibe as effective against Staphylococcus aureus and Escherichia coli ΔtolC. The addition of the efflux pump inhibitor PAβN enhanced daprodustat's efficacy against both bacteria and increased ezetimibe's potency against S. aureus. Molecular dynamics simulations confirmed stable drug binding to GroEL, supporting the antibacterial findings. The study demonstrates that computer-aided drug repurposing is a cost-effective strategy for discovering new therapeutic approaches, with potential applications in treating diseases like cancer, diabetes, and COVID-19.