Molecular Docking Study to Identify Potential AcrB Efflux Pump Inhibitors in Escherichia coli

The rapid emergence of MDR E. coli strains has posed a great challenge in human health, wherein the AcrB efflux pump acts as a crucial mediator of antibiotic resistance. Presented here is an in-depth computational analysis of three potent candidates-camalexin, 2-chloro-4-pyrrolidinopyridine, and 2,2-dimethylthiazolidine-along with Ciprofloxacin, an accepted antibiotic and target molecule of AcrB efflux pump (PDB ID: 4DX5) subjected simultaneously. By employing InstaDock v1.1 software for thorough molecular dock analysis, DS Visualizer software analysis, & SwissDrug Design software tools analysis of various data parameters including drug binding affinities, pharmacokinetic properties, polypharmacology predictions, & acute toxicity data (LD50 values), this analysis compares & contrasts computationally predicted data parameters of several drug candidates & Ciprofloxacin effectively. This analysis concludes that, in spite of Ciprofloxacin having a higher binding affinity, there are drug candidates that lead to superior pharmacokinetic properties & toxicity effects computationally, indicating the possibility of having a higher therapeutic index potentially. This result forms a rationale & hypothesis indicating the necessity of scrutinizing these newly identified drug candidates toward AcrB pump as a therapeutic strategy toward overcoming MDR in Escherichia coli effectively.