Peiter GC, de Souza CBT, de Oliveira LM, Pagliarin LG, dos Anjos VNF, da Silva FAF, de Melo FF, Teixeira KN. COVID-19 liver and gastroenterology findings: An in silico analysis of SARS-CoV-2 interactions with liver molecules. World J Hepatol 2022; 14(6): 1131-1141 [PMID: 35978663 DOI: 10.4254/wjh.v14.i6.1131]
Corresponding Author of This Article
Kádima Nayara Teixeira, PhD, Professor, Universidade Federal do Paraná, Campus Toledo, Road 182, Km 320/321, Toledo 85919-899, Paraná, Brazil. kadimateixeira@ufpr.br
Research Domain of This Article
Infectious Diseases
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 Hepatol. Jun 27, 2022; 14(6): 1131-1141 Published online Jun 27, 2022. doi: 10.4254/wjh.v14.i6.1131
COVID-19 liver and gastroenterology findings: An in silico analysis of SARS-CoV-2 interactions with liver molecules
Gabrielle Caroline Peiter, Cristiano de Bem Torquato de Souza, Lucca Miketen de Oliveira, Luis Gustavo Pagliarin, Valentina Nunes Fontoura dos Anjos, Filipe Antônio França da Silva, Fabrício Freire de Melo, Kádima Nayara Teixeira
Gabrielle Caroline Peiter, Cristiano de Bem Torquato de Souza, Lucca Miketen de Oliveira, Luis Gustavo Pagliarin, Valentina Nunes Fontoura dos Anjos, Kádima Nayara Teixeira, Universidade Federal do Paraná, Campus Toledo, Toledo 85919-899, Paraná, Brazil
Filipe Antônio França da Silva, Fabrício Freire de Melo, Universidade Federal da Bahia, Campus Anísio Teixeira, Vitória da Conquista 45029-094, Bahia, Brazil
Author contributions: Peiter GC, de Souza CBT, Oliveira LM, dos Anjos VNF and Pagliarin LG performed the experiments, analyzed the results and wrote the manuscript; da Silva FAF analyzed the results and reviewed the manuscript; de Melo FF performed a critical analysis of the results and corrected the manuscript; Teixeira KN interpreted the data, performed a critical analysis of the results, corrected the manuscript and coordinated the study; all authors approved the final version of the manuscript.
Institutional review board statement: The study did not need approval by the Research Ethics Committee as it was an in silico study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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, Road 182, Km 320/321, Toledo 85919-899, Paraná, Brazil. kadimateixeira@ufpr.br
Received: December 3, 2021 Peer-review started: December 3, 2021 First decision: February 8, 2022 Revised: February 22, 2022 Accepted: May 16, 2022 Article in press: May 16, 2022 Published online: June 27, 2022 Processing time: 202 Days and 1.9 Hours
ARTICLE HIGHLIGHTS
Research background
Coronavirus disease 19 (COVID-19) has variable clinical manifestations, including gastrointestinal and hepatic disorders. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects liver cells using angiotensin-converting enzyme 2, and the viral Spike glycoprotein must be cleaved by Furin or Type 2 Serine Protease. Following activation of the Akt/mTOR pathway several changes are triggered.
Research motivation
Liver damage in COVID-19 is not well understood; therefore, molecular analysis of the infection process and cell signaling, in silico, can help in the discovery of targets for treatment of the disease.
Research objectives
To analyze liver and gastrointestinal symptoms and cell signaling pathways triggered by SARS-CoV-2 infection due to virus-liver interactions in silico.
Research methods
SARS-CoV-2/liver cell interactions, and signaling pathways activated by these interactions, were analyzed by inhibition studies using the molecular docking method.
Research results
The mTORC1/CC-223 complex, Akt/MK-2206 complex and Furin/naphthofluorescein complex showed significant affinity energy, indicating stability and consequent effectiveness in inhibiting target molecules for COVID-19 therapy.
Research conclusions
Liver disease and signaling pathways altered by SARS-CoV-2 can be modulated by inhibitors that demonstrate significant affinity for interactions with human proteins, which could prevent progression of the infection and its symptoms.
Research perspectives
Evaluate the inhibition complexes studied using molecular dynamics and verify the possibility of structural changes of the drug to increase its efficiency and avoid possible adverse effects.
