Vieira RV, Peiter GC, de Melo FF, Zarpelon-Schutz AC, Teixeira KN. In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori. World J Clin Oncol 2024; 15(5): 653-663 [PMID: 38835850 DOI: 10.5306/wjco.v15.i5.653]
Corresponding Author of This Article
Kádima Nayara Teixeira, PhD, Professor, Universidade Federal do Paraná, Campus Toledo, Max Planck 3796, Toledo 85919-899, Brazil. kadimateixeira@ufpr.br
Research Domain of This Article
Chemistry, Medicinal
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. May 24, 2024; 15(5): 653-663 Published online May 24, 2024. doi: 10.5306/wjco.v15.i5.653
In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori
Rafaela Viana Vieira, Gabrielle Caroline Peiter, Fabrício Freire de Melo, Ana Carla Zarpelon-Schutz, Kádima Nayara Teixeira
Rafaela Viana Vieira, Ana Carla Zarpelon-Schutz, Kádima Nayara Teixeira, Universidade Federal do Paraná, Campus Toledo, Toledo 85919-899, Brazil
Gabrielle Caroline Peiter, Universidade Tecnológica Federal do Paraná, Campus Toledo, Paraná 85902-490, Brazil
Fabrício Freire de Melo, Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde-Campus Anísio Teixeira, Vitória da Conquista 45029-094, Brazil
Ana Carla Zarpelon-Schutz, Kádima Nayara Teixeira, Universidade Federal do Paraná-Setor Palotina, Programa de Pós-graduação em Biotecnologia, Palotina 85950-000, Brazil
Author contributions: Peiter GC performed the in silico experiments and analysis; Vieira RV and Teixeira KN interpreted the data and wrote the manuscript; Zarpelon-Schutz AC, de Melo FF and Teixeira KN performed the critical analysis of the results and coordinated the study; all authors approved the final version of the manuscript.
Institutional review board statement: Institutional review board declares awareness of the study and states that neither humans nor animals were involved in the research.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kádima Nayara Teixeira, PhD, Professor, Universidade Federal do Paraná, Campus Toledo, Max Planck 3796, Toledo 85919-899, Brazil. kadimateixeira@ufpr.br
Received: December 15, 2023 Revised: April 1, 2024 Accepted: April 18, 2024 Published online: May 24, 2024 Processing time: 157 Days and 13.1 Hours
Abstract
BACKGROUND
Colonization with Helicobacter pylori (H. pylori) has a strong correlation with gastric cancer, and the virulence factor CagA is implicated in carcinogenesis. Studies have been conducted using medicinal plants with the aim of eliminating the pathogen; however, the possibility of blocking H. pylori-induced cell differentiation to prevent the onset and/or progression of tumors has not been addressed. This type of study is expensive and time-consuming, requiring in vitro and/or in vivo tests, which can be solved using bioinformatics. Therefore, prospective computational analyses were conducted to assess the feasibility of interaction between phenolic compounds from medicinal plants and the CagA oncoprotein.
AIM
To perform a computational prospecting of the interactions between phenolic compounds from medicinal plants and the CagA oncoprotein of H. pylori.
METHODS
In this in silico study, the structures of the phenolic compounds (ligands) kaempferol, myricetin, quercetin, ponciretin (flavonoids), and chlorogenic acid (phenolic acid) were selected from the PubChem database. These phenolic compounds were chosen based on previous studies that suggested medicinal plants as non-drug treatments to eliminate H. pylori infection. The three-dimensional structure model of the CagA oncoprotein of H. pylori (receptor) was obtained through molecular modeling using computational tools from the I-Tasser platform, employing the threading methodology. The primary sequence of CagA was sourced from GenBank (BAK52797.1). A screening was conducted to identify binding sites in the structure of the CagA oncoprotein that could potentially interact with the ligands, utilizing the GRaSP online platform. Both the ligands and receptor were prepared for molecular docking using AutoDock Tools 4 (ADT) software, and the simulations were carried out using a combination of ADT and AutoDock Vina v.1.2.0 software. Two sets of simulations were performed: One involving the central region of CagA with phenolic compounds, and another involving the carboxy-terminus region of CagA with phenolic compounds. The receptor-ligand complexes were then analyzed using PyMol and BIOVIA Discovery Studio software.
RESULTS
The structure model obtained for the CagA oncoprotein exhibited high quality (C-score = 0.09) and was validated using parameters from the MolProbity platform. The GRaSP online platform identified 24 residues (phenylalanine and leucine) as potential binding sites on the CagA oncoprotein. Molecular docking simulations were conducted with the three-dimensional model of the CagA oncoprotein. No complexes were observed in the simulations between the carboxy-terminus region of CagA and the phenolic compounds; however, all phenolic compounds interacted with the central region of the oncoprotein. Phenolic compounds and CagA exhibited significant affinity energy (-7.9 to -9.1 kcal/mol): CagA/kaempferol formed 28 chemical bonds, CagA/myricetin formed 18 chemical bonds, CagA/quercetin formed 16 chemical bonds, CagA/ponciretin formed 13 chemical bonds, and CagA/chlorogenic acid formed 17 chemical bonds. Although none of the phenolic compounds directly bound to the amino acid residues of the K-Xn-R-X-R membrane binding motif, all of them bound to residues, mostly positively or negatively charged, located near this region.
CONCLUSION
In silico, the tested phenolic compounds formed stable complexes with CagA. Therefore, they could be tested in vitro and/or in vivo to validate the findings, and to assess interference in CagA/cellular target interactions and in the oncogenic differentiation of gastric cells.
Core Tip: Commonly, studies on the effects of medicinal plants on Helicobacter pylori (H. pylori) infection assess the antimicrobial activity of these plants. However, in this study, the authors conducted a prospective in silico analysis of the activity of certain phenolic compounds from plants used to treat H. pylori infection on stomach cells affected by CagA, aiming to prevent or block the oncogenic differentiation of these cells.
