Introduction of Novel Drug Targets Against Staphylococcus Aureus and Proposing Putative Inhibitors Against Adenine N1 (M1 A22)-Trna Methyltransferase (Trmk) Using Computer-Aided Drug Discovery

Introduction of Novel Drug Targets Against Staphylococcus Aureus and Proposing Putative Inhibitors Against Adenine N1 (M1 A22)-Trna Methyltransferase (Trmk) Using Computer-Aided Drug Discovery Publisher Pubmed

Beig M¹ ; Ebrahimi T² ; Goodarzi NN³ ; Fereshteh S¹ ; Habibi M⁴ ; Badmasti F^{1, 5}

Show Affiliations

1. Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
2. Department of Nanotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran
3. Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
4. Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran
5. Microbiology Research Center(MRC), Pasteur Institute of Iran, Tehran, Iran

Source: Current Pharmaceutical Design Published:2023

Abstract

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 core-proteome 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 AD-MET 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 Nocardio-azine_A, Geninthiocin_D, Citreamicin_delta, Quinaldopeptin, Rachelmycin, Di-AFN_A1 and Naphthomy-cin_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. © 2023 Bentham Science Publishers.

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Style	Citing Format
MLA	Beig M, et al.. "Introduction of Novel Drug Targets Against Staphylococcus Aureus and Proposing Putative Inhibitors Against Adenine N1 (M1 A22)-Trna Methyltransferase (Trmk) Using Computer-Aided Drug Discovery." Current Pharmaceutical Design, vol. 29, no. 14, 2023, pp. 1135-1147.
APA	Beig M, Ebrahimi T, Goodarzi NN, Fereshteh S, Habibi M, Badmasti F (2023). Introduction of Novel Drug Targets Against Staphylococcus Aureus and Proposing Putative Inhibitors Against Adenine N1 (M1 A22)-Trna Methyltransferase (Trmk) Using Computer-Aided Drug Discovery. Current Pharmaceutical Design, 29(14), 1135-1147.
Chicago	Beig M, Ebrahimi T, Goodarzi NN, Fereshteh S, Habibi M, Badmasti F. "Introduction of Novel Drug Targets Against Staphylococcus Aureus and Proposing Putative Inhibitors Against Adenine N1 (M1 A22)-Trna Methyltransferase (Trmk) Using Computer-Aided Drug Discovery." Current Pharmaceutical Design 29, no. 14 (2023): 1135-1147.
Harvard	Beig M et al. (2023) 'Introduction of Novel Drug Targets Against Staphylococcus Aureus and Proposing Putative Inhibitors Against Adenine N1 (M1 A22)-Trna Methyltransferase (Trmk) Using Computer-Aided Drug Discovery', Current Pharmaceutical Design, 29(14), pp. 1135-1147.
Vancouver	Beig M, Ebrahimi T, Goodarzi NN, Fereshteh S, Habibi M, Badmasti F. Introduction of Novel Drug Targets Against Staphylococcus Aureus and Proposing Putative Inhibitors Against Adenine N1 (M1 A22)-Trna Methyltransferase (Trmk) Using Computer-Aided Drug Discovery. Current Pharmaceutical Design. 2023;29(14):1135-1147.
BibTex	@article{ author = {Beig M and Ebrahimi T and Goodarzi NN and Fereshteh S and Habibi M and Badmasti F}, title = {Introduction of Novel Drug Targets Against Staphylococcus Aureus and Proposing Putative Inhibitors Against Adenine N1 (M1 A22)-Trna Methyltransferase (Trmk) Using Computer-Aided Drug Discovery}, journal = {Current Pharmaceutical Design}, volume = {29}, number = {14}, pages = {1135-1147}, year = {2023} }
RIS	TY - JOUR AU - Beig M AU - Ebrahimi T AU - Goodarzi NN AU - Fereshteh S AU - Habibi M AU - Badmasti F TI - Introduction of Novel Drug Targets Against Staphylococcus Aureus and Proposing Putative Inhibitors Against Adenine N1 (M1 A22)-Trna Methyltransferase (Trmk) Using Computer-Aided Drug Discovery JO - Current Pharmaceutical Design VL - 29 IS - 14 SP - 1135 EP - 1147 PY - 2023 ER -

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