Investigation of plant metabolites as potential inhibitors of Acinetobacter baumannii: An In-Silico approach

Abstract

The gram-negative bacteria Acinetobacter baumannii is responsible for a broad spectrum of dangerous nosocomial infections. Acinetobacter baumannii is easily transmitted into the body via mechanical ventilators, open wounds, and intravascular catheters. Bloodstream infections and ventilator-associated pneumonia caused by A. baumannii have the greatest mortality rates. Due to its multidrug resistance (MDR), broad drug resistance, and pan-drug resistance phenotypes, A. baumannii is now recognized as a particularly challenging pathogen to control. In order to develop novel therapeutics for the existing condition, an in-silico approach was used. Based on the review of the literature, five drug target proteins including OmpA (Peptidoglycan-binding domain), CarO, DcaP, OmpW, and PBP were identified to be vital for the pathogen's survival, infection to the host, and multidrug resistance. A total of 20 potential plant metabolites with antibacterial properties were docked against these proteins. Among them, Corilagin, (+)-Lyoniresinol-3 alpha-O-beta-d-glucopyranoside, Epsilon-Viniferin, and Epigallocatechin gallate (EGCG) showed superior binding energy compared to the reference drug carbapenem. Corilagin and -(+)-Lyoniresinol-3 alpha-O-beta-d-glucopyranoside showed the best binding energy with DcaP protein having a docking score of about −261.74, and −238.19 respectively. Those two best protein-ligand complexes were assessed for MD simulation where the average RMSD value of 3.5 A° for Dcap-Corilagin and 3.0 A° for Dcap-(+)-Lyoniresinol-3 alpha-O-beta-d-glucopyranoside indicated their excellent stability. In-silico ADME analysis showed all four metabolites had a good estimated solubility (ESOL) between −3.56 and −6.32, a Log P range of 1.87–2.71 and they responded negatively in Blood-Brain Barrier, and CYP inhibition. Toxicity study showed that the expected new drugs, particularly Corilagin, are completely non-carcinogenic, non-toxic, and safe to use as therapeutic treatments against Acinetobacter baumannii. Therefore, all the predicted four metabolites could be used as a medication against Acinetobacter baumannii. As a result of the promising outcomes from our present study, we strongly recommend more in vivo analysis for experimental confirmation.