Identification of Novel Drug Targets in Porphyromonas Gingivalis and Proposing Inhibitors Against Acetate Kinase Using Structure-Based Virtual Screening

Identification of Novel Drug Targets in Porphyromonas Gingivalis and Proposing Inhibitors Against Acetate Kinase Using Structure-Based Virtual Screening Publisher

Kalhor H¹ ; Noori Goodarzi N² ; Rahimi H^{3, 4} ; Firoozeh F⁵ ; Badmasti F^{6, 7}

Show Affiliations

1. Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
2. Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
3. Texas Biomedical Research Institute, San Antonio, 78227, TX, United States
4. Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
5. Department of Microbiology, School of Medicine, Alborz University of Medical Science, Karaj, Iran
6. Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
7. Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran

Source: Process Biochemistry Published:2023

Abstract

Porphyromonas gingivalis is the conductor of the orchestration of periodontium inflammation. Considering that a wide range of antibiotics have lost their activities in the last century, this study aimed to introduce novel and broad-spectrum drug targets against this pathogen. For this purpose, the core proteins of 17 P. gingivalis strains were obtained. Out of 1418 core proteins, 166 cytoplasmic, essential factors with no sequence similarity to host were selected. Fifty-two P. gingivalis metabolome-specific proteins were detected and then 31 novel drug targets were identified using the DrugBank database. Finally, nine broad-spectrum, novel drug targets were introduced. Acetate kinase (Ack) was selected as a novel target for drug discovery procedure due to the crucial role of this protein in the survival of P. gingivalis. Subsequently, structure-based virtual screening revealed six lead compounds with the most desirable features. Neoagarohexaose, Lucensomycin, Tetrafibricin, Naquihexcin_H, Tetramycin_A, and Platensimycin_D. Interestingly, Platensimycin_D1 had highest drug-likeness features in comparison to other lead compounds. While, Tetramycin_A and Lucensomycin showed better ADMET properties. The hit compounds identified here would be an initial compounds for experimental susceptibility testing against this pathogen. In addition, these findings might help out with the future studies on development of new therapeutic agents against P. gingivalis. © 2023 Elsevier Ltd

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Style	Citing Format
MLA	Kalhor H, et al.. "Identification of Novel Drug Targets in Porphyromonas Gingivalis and Proposing Inhibitors Against Acetate Kinase Using Structure-Based Virtual Screening." Process Biochemistry, vol. 130, no. , 2023, pp. 310-321.
APA	Kalhor H, Noori Goodarzi N, Rahimi H, Firoozeh F, Badmasti F (2023). Identification of Novel Drug Targets in Porphyromonas Gingivalis and Proposing Inhibitors Against Acetate Kinase Using Structure-Based Virtual Screening. Process Biochemistry, 130(), 310-321.
Chicago	Kalhor H, Noori Goodarzi N, Rahimi H, Firoozeh F, Badmasti F. "Identification of Novel Drug Targets in Porphyromonas Gingivalis and Proposing Inhibitors Against Acetate Kinase Using Structure-Based Virtual Screening." Process Biochemistry 130, no. (2023): 310-321.
Harvard	Kalhor H et al. (2023) 'Identification of Novel Drug Targets in Porphyromonas Gingivalis and Proposing Inhibitors Against Acetate Kinase Using Structure-Based Virtual Screening', Process Biochemistry, 130(), pp. 310-321.
Vancouver	Kalhor H, Noori Goodarzi N, Rahimi H, Firoozeh F, Badmasti F. Identification of Novel Drug Targets in Porphyromonas Gingivalis and Proposing Inhibitors Against Acetate Kinase Using Structure-Based Virtual Screening. Process Biochemistry. 2023;130():310-321.
BibTex	@article{ author = {Kalhor H and Noori Goodarzi N and Rahimi H and Firoozeh F and Badmasti F}, title = {Identification of Novel Drug Targets in Porphyromonas Gingivalis and Proposing Inhibitors Against Acetate Kinase Using Structure-Based Virtual Screening}, journal = {Process Biochemistry}, volume = {130}, number = {}, pages = {310-321}, year = {2023} }
RIS	TY - JOUR AU - Kalhor H AU - Noori Goodarzi N AU - Rahimi H AU - Firoozeh F AU - Badmasti F TI - Identification of Novel Drug Targets in Porphyromonas Gingivalis and Proposing Inhibitors Against Acetate Kinase Using Structure-Based Virtual Screening JO - Process Biochemistry VL - 130 IS - SP - 310 EP - 321 PY - 2023 ER -

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