Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Jul 27, 2023; 14(4): 72-83
Published online Jul 27, 2023. doi: 10.4331/wjbc.v14.i4.72
In silico evidence of Remdesivir action in blood coagulation cascade modulation in COVID-19 treatment
Luis Gustavo Pagliarin, Lucca Miketen de Oliveira, Valentina Nunes Fontoura dos Anjos, Cristiano de Bem Torquato de Souza, Gabrielle Caroline Peiter, Cinthia Façanha Wendel, Anderson Dillmann Groto, Fabrício Freire de Melo, Kádima Nayara Teixeira
Luis Gustavo Pagliarin, Lucca Miketen de Oliveira, Valentina Nunes Fontoura dos Anjos, Cristiano de Bem Torquato de Souza, Cinthia Façanha Wendel, Anderson Dillmann Groto, Kádima Nayara Teixeira, Campus Toledo, Universidade Federal do Paraná, Toledo 85.919-899, Paraná, Brazil
Gabrielle Caroline Peiter, Kádima Nayara Teixeira, Programa Multicêntrico de Pós-graduação em Bioquímica e Biologia Molecular - Setor Palotina, Universidade Federal do Paraná, Palotina 85.950-000, Paraná, Brazil
Fabrício Freire de Melo, Instituto Multidisciplinar em Saúde - Campus Anísio Teixeira, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
Author contributions: Pagliarin LG, Oliveira LM, Anjos VNF, and Souza CBT performed the experiments, analyzed the results, and wrote the manuscript; Peiter GC, Wendel CF, and Groto AD performed the experiments; Melo FF performed the critical analysis of the results; Teixeira KN interpreted the data, performed the 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: This study used data from three-dimensional structures deposited in public online databases.
Conflict-of-interest statement: The authors state that there is no conflict of interest of any kind with regard to this study.
Data sharing statement: This study was developed in silico and no patient data or data from medical records were used in this study.
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, Campus Toledo, Universidade Federal do Paraná, Max Planck 3796, Toledo 85.919-899, Paraná, Brazil. kadimateixeira@ufpr.br
Received: December 30, 2022
Peer-review started: December 30, 2022
First decision: April 13, 2023
Revised: April 30, 2023
Accepted: July 3, 2023
Article in press: July 3, 2023
Published online: July 27, 2023
ARTICLE HIGHLIGHTS
Research background

The need for a treatment for coronavirus disease 2019 (COVID-19) has prompted some commercial drugs to be tested off-label. The evaluation of off-label drugs has provided incomplete information about their efficacy and gaps about long-term and chronic adverse effects. Remdesivir is an example of an off-label drug that showed promising results in the treatment of COVID-19, but may have other benefits that have not been explored and could be studied in silico.

Research motivation

The motivation for this study arose from the need to provide data that could help inform studies on Remdesivir, since this drug has not been evaluated through standard clinical trials for COVID-19. Remdesivir has met clinical trials for the treatment of another viral disease, and when used for the treatment of a different disease, both benefits and side effects can arise. Since our team observed the affinity of this antiviral for clotting factors in silico, we hypothesized that it might have benefits not only for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but also for treating symptoms of severe COVID-19, such as disseminated intravascular coagulation.

Research objectives

The aim of the research was to evaluate whether Remdesivir has interaction affinity with clotting factors and to compare these interactions with the interaction with key receptors in SARS-CoV-2 infection to infer possible pharmacological activities.

Research methods

The study was performed in a computational environment using molecular docking and bioinformatics tools that allow to mimic the rational behavior of Remdesivir based on its chemical characteristics. The affinity energy and chemical bonds of Remdesivir with target molecules were analyzed and used to extrapolate in silico information to the human physiological environment.

Research results

The in silico results on the activity of Remdesivir in the coagulation cascade are promising when considering severe cases of COVID-19, but they need to be evaluated in vivo. In silico data show that Remdesivir can bind to various clotting factors with different affinities; this suggests that this drug can prevent coagulation by acting at several distinct points of the cascade, which increases its effectiveness when disseminated intravascular coagulation is triggered by viral infection.

Research conclusions

Our research team suggests that Remdesivir may be an off-label drug used as an antiviral for the treatment of COVID-19, but it can also be used to treat severe symptoms of the disease; however, this needs to be confirmed by in vivo testing.

Research perspectives

The research perspective is to evaluate, in silico, other off-label drugs suggested for the treatment of COVID-19.