Considering the adverse effect of antimicrobial resistance (AMR) crisis on human life, there is an immediate need for finding new alternative drugs for treatment of emerging infectious diseases. Therapeutic options, including last-line or combined antibiotic therapies for Acinetobacter baumannii, as a multi-drug resistant (MDR) human pathogen responsible for severe nosocomial and several other infections, are apparently ineffective. The outer membrane protein A (OmpA) and outer membrane protein W (OmpW) are two porins known for their different cellular functions. Identification of natural compounds with potentials to block these putative porins can possibly attenuate the growth of the bacteria and control the relating diseases. The current work aimed to screen a library of 384 phytochemicals according to their potentials to be used as a drug, and potentials to inhibit the function of OmpA and OmpW in A. baumannii. Although the anti-virulence activities of these biomolecules are reported previously, no evaluation of their effect on functional aspects of OmpA and OmpW in A. baumannii has been performed so far. In this study, the phytocompounds were initially screened based on their physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) drug-like properties. Afterwards, the selected ligands were subjected to standard docking calculations against predicted three-dimensional structure of OmpA and OmpW in A. baumannii. We identified three phytochemicals (isosakuranetin, aloe-emodin and pinocembrin) bearing appreciable binding affinity towards the selected binding pocket of OmpA and OmpW. Molecular dynamics (MD) simulation analysis confirmed the stability of the complexes. Amongst them, isosakuranetin was suggested as the best phytocompounds for further in vitro and in vivo study.

Data were collected using software analysis. More details are given in the article with the same title.