A comprehensive computational study to explore promising natural bioactive compounds targeting glycosyltransferase MurG in Escherichia coli for potential drug development

Amneh Shtaiwi, Shafi Ullah Khan, Meriem Khedraoui, Mohd Alaraj, Abdelouahid Samadi, Samir Chtita

Research output: Contribution to journalArticlepeer-review

Abstract

Peptidoglycan is a carbohydrate with a cross-linked structure that protects the cytoplasmic membrane of bacterial cells from damage. The mechanism of peptidoglycan biosynthesis involves the main synthesizing enzyme glycosyltransferase MurG, which is known as a potential target for antibiotic therapy. Many MurG inhibitors have been recognized as MurG targets, but high toxicity and drug-resistant Escherichia coli strains remain the most important problems for further development. In addition, the discovery of selective MurG inhibitors has been limited to the synthesis of peptidoglycan-mimicking compounds. The present study employed drug discovery, such as virtual screening using molecular docking, drug likeness ADMET proprieties predictions, and molecular dynamics (MD) simulation, to identify potential natural products (NPs) for Escherichia coli. We conducted a screening of 30,926 NPs from the NPASS database. Subsequently, 20 of these compounds successfully passed the potency, pharmacokinetic, ADMET screening assays, and their validation was further confirmed through molecular docking. The best three hits and the standard were chosen for further MD simulations up to 400 ns and energy calculations to investigate the stability of the NPs-MurG complexes. The analyses of MD simulations and total binding energies suggested the higher stability of NPC272174. The potential compounds can be further explored in vivo and in vitro for promising novel antibacterial drug discovery.

Original languageEnglish
Article number7098
JournalScientific reports
Volume14
Issue number1
DOIs
Publication statusPublished - Dec 2024

Keywords

  • Antibacterial
  • Antibiotics resistance
  • Escherichia coli
  • Molecular dynamics
  • MurG
  • Natural products
  • Virtual screening

ASJC Scopus subject areas

  • General

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