Exploring North African Plant Metabolites as Potential Agents for Acinetobacter baumannii Infection Control: An In Silico Study Targeting the AbaR Receptor

ABSTRACT Acinetobacter baumannii is classified by the World Health Organization as a priority pathogen due to its multidrug resistance. Its ability to form biofilms and persist on abiotic surfaces enhances environmental survival and transmission, complicating infection control. Since quorum sensing (QS) regulates these virulence traits, targeting QS represents a promising anti‐virulence strategy. We analyzed 594 A. baumannii isolates and found the abaR gene, encoding the QS receptor AbaR, in 88.39% of them, with a highly conserved active site. This conservation underscores AbaR as a broadly relevant therapeutic target. Using structure‐based pharmacophore modeling and virtual screening of plant metabolites from the North African Natural Products Database (NANPDB), we identified several candidate inhibitors. Molecular docking and molecular dynamics simulations highlighted Epoformin as a potential AbaR ligand that stabilizes the receptor in an inactive conformation. Low RMSD and RMSF values, together with favorable radius of gyration (Rg) and solvent‐accessible surface area (SASA) profiles, confirmed a stable binding, with consistent interactions at key residues. In silico ADMET profiling indicated acceptable drug‐likeness and no major predicted liabilities. By inhibiting AbaR‐mediated QS, these compounds could disrupt biofilm formation and reduce A. baumannii transmission on surfaces. Although these computational results are promising for anti‐virulence therapy development, experimental validation is necessary to confirm efficacy and potential clinical use.