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Research Article

Introduction of Novel Drug Targets against <i>Staphylococcus aureus</i> and Proposing Putative Inhibitors against Adenine N1 (m<sup>1</sup>A22)-tRNA Methyltransferase (TrmK) using Computer-aided Drug Discovery

[ Vol. 29 , Issue. 14 ]


Masoumeh Beig, Tahereh Ebrahimi, Narjes Noori Goodarzi, Sepideh Fereshteh, Mehri Habibi and Farzad Badmasti*   Pages 1135 - 1147 ( 13 )


Background: Nowadays, the emergence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) strains has dramatically restricted the treatment options against this microorganism.

Aim: In this study, we aimed to discover new drug targets and inhibitors against S. aureus.

Methods: This study consists of two major sections. In the upstream evaluation, after a comprehensive coreproteome analysis, essential cytoplasmic proteins with no similarity to the human proteome were selected. Then the S. aureus metabolome-specific proteins were selected, and novel drug targets were identified using the DrugBank database. In the downstream analysis, a structure-based virtual screening approach was performed to reveal potential hit compounds against adenine N1 (m1A22)-tRNA methyltransferase (TrmK) using the StreptomeDB library and AutoDock Vina software. The compounds with a binding affinity > -9 kcal/mol were analyzed based on ADMET properties. Finally, the hit compounds were selected based on Lipinski’s rule of five (RO5).

Results: Three proteins, including glycine glycosyltransferase (FemA), TrmK, and heptaprenyl pyrophosphate synthase subunit A (HepS1), were selected as feasible and promising drug targets based on PDB file availability and their essential role in the survival of the S. aureus. Finally, seven hit compounds, including Nocardioazine_ A, Geninthiocin_D, Citreamicin_delta, Quinaldopeptin, Rachelmycin, Di-AFN_A1 and Naphthomycin_ K were introduced against the binding cavity of TrmK, as a feasible drug target.

Conclusion: The results of this study provided three feasible drug targets against S. aureus. In the following, seven hit compounds were introduced as potential inhibitors of TrmK, and Geninthiocin_D was identified as the most desirable agent. However, in vivo and in vitro investigations are needed to confirm the inhibitory effect of these agents on S. aureus.


<i>Staphylococcus aureus</i>, structure-based virtual screening, TrmK, Quinaldopeptin, ADMET, VRSA.


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