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ORIGINAL RESEARCH article

Front. Bioinform.
Sec. Drug Discovery in Bioinformatics
Volume 4 - 2024 | doi: 10.3389/fbinf.2024.1482338

Identification of Novel Drug Targets for Helicobacter pylori: Structure-Based Virtual Screening of Potential Inhibitors against DAH7PS protein Involved in the Shikimate Pathway

Provisionally accepted
Narjes Noori Goodarzi Narjes Noori Goodarzi 1,2Mahshid Khazani Asforooshani Mahshid Khazani Asforooshani 1,3Behzad Shahbazi Behzad Shahbazi 4Nayereh Rezaie Rahimi Nayereh Rezaie Rahimi 1,5Farzad Badmasti Farzad Badmasti 1*
  • 1 Pasteur Institute of Iran (PII), Tehran, Tehran, Iran
  • 2 Tehran University of Medical Sciences, Tehran, Tehran, Iran
  • 3 Alzahra University, Tehran, Tehran, Iran
  • 4 Semnan University of Medical Sciences, Semnan, Semnan, Iran
  • 5 Shiraz University of Medical Sciences, Shiraz, Fars, Iran

The final, formatted version of the article will be published soon.

    Background: Helicobacter pylori, a bacterium associated with severe gastrointestinal diseases and malignancies, poses a significant challenge because of its increasing antibiotic resistance rates. This study aimed to identify potential drug targets and inhibitors against H. pylori using a structure-based virtual screening (SBVS) approach.Methods: Core-proteome analysis of 132 H. pylori genomes was performed using the EDGAR database. Essential genes were identified and human and gut microbiota homolog proteins were excluded. The DAH7PS protein involved in the shikimate pathway was selected for the structure-based virtual screening (SBVS) approach. The tertiary structure of the protein was predicted through homology modeling (based on PDB ID: 5UXM). Molecular docking was performed to identify potential inhibitors of DAH7PS among StreptomeDB compounds using the AutoDock Vina tool. Molecular dynamics (MD) simulations assessed the stability of DAH7PS-ligand complexes. The complexes were further evaluated in terms of their binding affinity, Lipinski's Rule of Five, and ADMET properties.Results: A total of 54 novel drug targets with desirable properties were identified. DAH7PS was selected for further investigation, and virtual screening of StreptomeDB compounds yielded 36 high-affinity binding of the ligands. Two small molecules, 6,8-Dihydroxyisocoumarin-3-carboxylic acid and Epicatechin, also showed favorable RO5 and ADMET properties. MD simulations confirmed the stability and reliability of DAH7PS-ligand complexes, indicating their potential as inhibitors.This study identified 54 novel drug targets against H. pylori. The DAH7PS protein as a promising drug target was evaluated using a computer-aided drug design. 6,8-Dihydroxyisocoumarin-3-carboxylic acid and Epicatechin demonstrated desirable properties and stable interactions, highlighting their potential to inhibit DAH7PS as an essential protein.Undoubtedly, more experimental validations are needed to advance these findings into practical therapies for treating drug-resistant H. pylori.

    Keywords: Helicobacter pylori, Structure-based virtual screening, Shikimate Pathway, DAH7PS, StreptomeDB

    Received: 18 Aug 2024; Accepted: 07 Oct 2024.

    Copyright: © 2024 Noori Goodarzi, Khazani Asforooshani, Shahbazi, Rezaie Rahimi and Badmasti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Farzad Badmasti, Pasteur Institute of Iran (PII), Tehran, Tehran, Iran

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.