IN-SILICO IDENTIFICATION OF NATURAL COMPOUND AS QUORUM SENSING INHIBITORS AGAINST PSEUDOMONAS AERUGINOSA

Abstract

Pseudomonas aeruginosa ’s virulence and the formation of biofilms are controlled via quorum sensing (QS), a crucial intercellular interaction mechanism that greatly contributes to the bacteria’s resistance to drugs. A possible anti-virulence tactic to get beyond traditional antibiotic pressure is to target the LasR receptor, a key transcriptional regulator of the QS system. In order to find effective LasR inhibitors, a thorough in silico screening of a library of 4,431 naturally occurring chemicals was carried out. PyRx was employed to perform molecular docking, and the technique was verified using two well-known inhibitors, Quercetin and Isorhamnetin, which demonstrated binding affinities of -10.5 and -10.4 kcal/mol, respectively. With an exceptionally lowest binding affinity of (-13.4 kcal/mol), virtual screening revealed Aotaphenazine as a superior lead candidate, much surpassing the clinical control, Ciprofloxacin (-7.9 kcal/mol). Aotaphenazine ’s pharmacokinetic viability and drug likeness were validated by further ADME profiling, supporting its promise as a bioavailable therapeutic agent. These results establish Aotaphenazine as a potent new anti-virulence lead candidate, offering a solid basis for additional in vitro validation and the creation of innovative therapies against P. aeruginosa infections.