The repurposing of recently approved US-FDA drugs against Gram-negative bacteria's biofilm-forming proteins

Gram-negative bacteria are a significant source of global illness and acquire antimicrobial resistance more rapidly than Gram-positive bacteria. Approximately 60–80% of bacterial resistances are caused by biofilms. The biofilm-associated common drug-resistant Gram-negative bacteria are Actinobacter baumannii, Pseudomonas aeruginosa , and Escherichia coli . The main goal of the current investigation is to repurpose recently FDA-approved drugs against Gram-negative biofilms. Ligand compounds were selected from FDA-approved drug lists from the past five years. Targets were identified through literature studies and obtained from the Protein Data Bank. After the molecular docking, 11 drugs showed binding conformations with energetically favorable interactions within the active sites of the targets. Three drugs were selected for further analysis based on a docking score (≤ -7). These drugs were then subjected to MM-GBSA and molecular dynamics studies. From the molecular dynamics assessments, two drugs including bempedoic acid and Siponimod were found to be dynamically stable in the active site of the biofilm-promoting protein of Escherichia coli . The identified drugs have exhibited promising potential for being repurposed as therapeutic agents against resistant Gram-negative bacteria. This suggests that these drugs, originally developed for other indications, may be effective in addressing the challenge of antibiotic resistance in Gram-negative bacteria. However, experimental studies are required to confirm their antibacterial potential.