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Updated: Jun 1, 2026
Assay Development for High-Throughput Drug Screening Against Mycobacteria
Published on: October 25, 2024
Virtual screening for potential inhibitors of bacterial MurC and MurD ligases
Tihomir Tomašić1, Andreja Kovač, Gerhard Klebe
1Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
Abstract:
Mur ligases are bacterial enzymes involved in the cytoplasmic steps of peptidoglycan biosynthesis and are viable targets for antibacterial drug discovery. We have performed virtual screening for potential ATP-competitive inhibitors targeting MurC and MurD ligases, using a protocol of consecutive hierarchical filters. Selected compounds were evaluated for inhibition of MurC and MurD ligases, and weak inhibitors possessing dual inhibitory activity have been identified. These compounds represent new scaffolds for further optimisation towards multiple Mur ligase inhibitors with improved inhibitory potency.
Insights
Researchers screened for antibacterial compounds targeting Mur ligases, essential bacterial enzymes. Weak dual inhibitors of MurC and MurD were found, offering new scaffolds for developing potent, multi-target antibacterial drugs.
Area of Science:
- Biochemistry
- Enzymology
- Drug Discovery
Background:
- Bacterial peptidoglycan biosynthesis relies on Mur ligases.
- Mur ligases are crucial targets for novel antibacterial agents.
- Identifying inhibitors of MurC and MurD is key for drug development.
Purpose of the Study:
- To identify ATP-competitive inhibitors of MurC and MurD ligases.
- To explore virtual screening methods for antibacterial drug discovery.
- To find novel chemical scaffolds for multi-target Mur ligase inhibitors.
Main Methods:
- Virtual screening using hierarchical filters.
- In vitro evaluation of selected compounds against MurC and MurD.
- Structure-activity relationship analysis for optimization.
Main Results:
- Identified weak dual inhibitors targeting both MurC and MurD ligases.
- Discovered new chemical scaffolds with potential for optimization.
- Demonstrated the feasibility of targeting multiple Mur ligases.
Conclusions:
- The identified compounds are promising starting points for developing broad-spectrum antibacterial drugs.
- Further optimization can lead to potent inhibitors of Mur ligases.
- Targeting multiple Mur ligases simultaneously offers a strategy to combat bacterial resistance.
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