Background: The prevalence of multi-drug resistance S. aureus is one of the most challenging
tasks for the treatment of nosocomial infections. Proteins and enzymes of peptidoglycan biosynthesis
pathway are one among the well-studied targets, but many of the enzymes are unexplored as targets.
MurE is one such enzyme featured to be a promising target. As MurE plays an important role in ligating
the L-lys to stem peptide at third position that is crucial for peptidoglycan synthesis.
Objective: To screen the potential MurE inhibitor by in silico approach and evaluate the best potential
lead molecule by in vitro methods.
Method: In the current study, we have employed structure based virtual screening targeting the active
site of MurE, followed by Molecular dynamics and in vitro studies.
Results: Virtual screening resulted in successful screening of potential lead molecule ((2R)-2-[[1-[(2R)-
2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan). The molecular
dynamics of the MurE and Lead molecule complex emphasizes that lead molecule has shown
stable interactions with active site residues Asp 406 and with Glu 460. In vitro studies demonstrate that
the lead molecule shows antibacterial activity close to standard antibiotic Vancomycin and higher than
that of Ampicillin, Streptomycin and Rifampicin. The MIC of lead molecule at 50g/mL was observed
to be 3.75 g/mL, MBC being bactericidal with value of 6.25 μg/mL, cytotoxicity showing 34.44% and
Conclusion: These results suggest ((2R)-2-[[1-[(2R)-2-(benzyloxycarbonylamino) propanoyl]
piperidine-4-carbonyl]amino]-5-guanidino-pentan) as a promising lead molecule for developing a MurE
inhibitor against treatment of S. aureus infections.