Screening of anti-Acinetobacter baumannii plant-based compounds, based on potential inhibition of OmpA and OmpW functions

Considering the adverse effect of antimicrobial resistance (AMR) crisis on
human life, there is an immediate need for finding new alternatives for
treatment of emerging infectious diseases. Therapeutic options, including
last-line or combined antibiotic therapies for Acinetobacter baumannii, as
an emergent 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 as virulence factors with different
cellular functions. Identification of natural compounds with potentials to
block these putative virulence factors can possibly attenuate the growth
of the bacteria and control the relating diseases. The current work aimed
to screen the therapeutic potential of a library of 371 phytochemicals, as
multi-blockers of OmpA and OmpW in A. baumannii. Although the
anti-virulence activities of these biomolecules are reported previously,
no evaluation on A. baumannii has been performed so far. Moreover, there
is no safety screening and early alerts of these compounds. In this study,
hits were initially selected 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 five phytochemicals (Amorphigenin
(PUBCHEM CID 92207), Bisdemethoxy-curcumin (PUBCHEM CID 5315472), Dalbinol
(PUBCHEM CID 44257412), Epicatechin gallate (PUBCHEM CID 72276) and
Nordihydroguaiaretic acid (PUBCHEM CID 4534)) bearing appreciable binding
affinity towards the selected binding pocket of OmpA and OmpW.