A target-guided drug repurposing strategy for antibacterial discovery - PubMed
4 hours ago
- #Antibacterial
- #Drug Repurposing
- #Molecular Docking
- A target-guided drug repurposing (DR) strategy was developed to address the scarcity of effective antibiotics against drug-resistant pathogens.
- Molecular docking was performed between 125 bacterial essential proteins and 2,027 approved non-antibacterial drugs to predict interactions.
- 14 candidate drugs were screened against six bacterial strains, with some showing inhibitory activity at 100 μg/ml.
- Lower-concentration assays combined with Polymyxin B nonapeptide (PMBN) were conducted for active drugs.
- Several non-antibacterial drugs exhibited antibacterial activities, and existing antibacterials were clustered based on binding affinity.
- Lifitegrast (8 μg/ml) combined with PMBN effectively inhibited six gram-negative bacteria.
- Folate rescue experiments indicated that lifitegrast's mechanism involves inhibiting FolA function.
- Future research should explore lifitegrast's structure-activity relationship and its impact on antibacterial activity.