Repurposing Existing FDA-Approved Medications by Virtual Screening for Combatting Pseudomonas aeruginosa Infections

Abstract

Pseudomonas aeruginosa, a notorious pathogen, poses significant challenges due to its resistance to multiple antibiotics. This study aims to identify potential FDA-approved drugs that could be repurposed to combat P. aeruginosa infections through virtual screening. The target protein, DNA gyrase B 24kDa ATPase subdomain (PDB ID: 7PTF), was refined using PDBREDO, improving geometric parameters despite a slight increase in R and R-free values. The virtual screening revealed several promising candidates with high binding affinities, including acetyldigitoxin (-9.9), digoxin (-9.5), digitoxin (-9.4), posaconazole (-9.3), venetoclax (-8.8), and itraconazole (-8.7). These top hits, primarily comprising cardiac glycosides and antifungal agents, exhibited large molecular weights, numerous hydrogen bond donors and acceptors, and significant molecular flexibility. The findings suggest potential repurposing opportunities for these drugs in treating P. aeruginosa infections, warranting further in-vitro and in-vivo investigations to validate their antimicrobial efficacy.