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Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches
Diminazene aceturate (DIZE), an antiparasitic, is an ACE2 activator, and studies show that activators of this enzyme may be beneficial for COVID-19, disease caused by SARS-CoV-2. Thus, the objective was to evaluate the in silico and in vitro affinity of diminazene aceturate against molecular targets...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier B.V.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476334/ https://www.ncbi.nlm.nih.gov/pubmed/36116513 http://dx.doi.org/10.1016/j.cbi.2022.110161 |
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author | Santos, Esley S. Silva, Priscila C. Sousa, Paulo S.A. Aquino, Cristhyane C. Pacheco, Gabriella Teixeira, Luiz F.L.S. Araujo, Alyne R. Sousa, Francisca B.M. Barros, Romulo O. Ramos, Ricardo M. Rocha, Jefferson A. Nicolau, Lucas A.D. Medeiros, Jand V.R. |
author_facet | Santos, Esley S. Silva, Priscila C. Sousa, Paulo S.A. Aquino, Cristhyane C. Pacheco, Gabriella Teixeira, Luiz F.L.S. Araujo, Alyne R. Sousa, Francisca B.M. Barros, Romulo O. Ramos, Ricardo M. Rocha, Jefferson A. Nicolau, Lucas A.D. Medeiros, Jand V.R. |
author_sort | Santos, Esley S. |
collection | PubMed |
description | Diminazene aceturate (DIZE), an antiparasitic, is an ACE2 activator, and studies show that activators of this enzyme may be beneficial for COVID-19, disease caused by SARS-CoV-2. Thus, the objective was to evaluate the in silico and in vitro affinity of diminazene aceturate against molecular targets of SARS-CoV-2. 3D structures from DIZE and the proteases from SARS-CoV-2, obtained through the Protein Data Bank and Drug Database (Drubank), and processed in computer programs like AutodockTools, LigPlot, Pymol for molecular docking and visualization and GROMACS was used to perform molecular dynamics. The results demonstrate that DIZE could interact with all tested targets, and the best binding energies were obtained from the interaction of Protein S (closed conformation −7.87 kcal/mol) and M(pro) (−6.23 kcal/mol), indicating that it can act both by preventing entry and viral replication. The results of molecular dynamics demonstrate that DIZE was able to promote a change in stability at the cleavage sites between S1 and S2, which could prevent binding to ACE2 and fusion with the membrane. In addition, in vitro tests confirm the in silico results showing that DIZE could inhibit the binding between the spike receptor-binding domain protein and ACE2, which could promote a reduction in the virus infection. However, tests in other experimental models with in vivo approaches are needed. |
format | Online Article Text |
id | pubmed-9476334 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94763342022-09-15 Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches Santos, Esley S. Silva, Priscila C. Sousa, Paulo S.A. Aquino, Cristhyane C. Pacheco, Gabriella Teixeira, Luiz F.L.S. Araujo, Alyne R. Sousa, Francisca B.M. Barros, Romulo O. Ramos, Ricardo M. Rocha, Jefferson A. Nicolau, Lucas A.D. Medeiros, Jand V.R. Chem Biol Interact Research Paper Diminazene aceturate (DIZE), an antiparasitic, is an ACE2 activator, and studies show that activators of this enzyme may be beneficial for COVID-19, disease caused by SARS-CoV-2. Thus, the objective was to evaluate the in silico and in vitro affinity of diminazene aceturate against molecular targets of SARS-CoV-2. 3D structures from DIZE and the proteases from SARS-CoV-2, obtained through the Protein Data Bank and Drug Database (Drubank), and processed in computer programs like AutodockTools, LigPlot, Pymol for molecular docking and visualization and GROMACS was used to perform molecular dynamics. The results demonstrate that DIZE could interact with all tested targets, and the best binding energies were obtained from the interaction of Protein S (closed conformation −7.87 kcal/mol) and M(pro) (−6.23 kcal/mol), indicating that it can act both by preventing entry and viral replication. The results of molecular dynamics demonstrate that DIZE was able to promote a change in stability at the cleavage sites between S1 and S2, which could prevent binding to ACE2 and fusion with the membrane. In addition, in vitro tests confirm the in silico results showing that DIZE could inhibit the binding between the spike receptor-binding domain protein and ACE2, which could promote a reduction in the virus infection. However, tests in other experimental models with in vivo approaches are needed. Elsevier B.V. 2022-11-01 2022-09-15 /pmc/articles/PMC9476334/ /pubmed/36116513 http://dx.doi.org/10.1016/j.cbi.2022.110161 Text en © 2022 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Research Paper Santos, Esley S. Silva, Priscila C. Sousa, Paulo S.A. Aquino, Cristhyane C. Pacheco, Gabriella Teixeira, Luiz F.L.S. Araujo, Alyne R. Sousa, Francisca B.M. Barros, Romulo O. Ramos, Ricardo M. Rocha, Jefferson A. Nicolau, Lucas A.D. Medeiros, Jand V.R. Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches |
title | Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches |
title_full | Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches |
title_fullStr | Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches |
title_full_unstemmed | Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches |
title_short | Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches |
title_sort | antiviral potential of diminazene aceturate against sars-cov-2 proteases using computational and in vitro approaches |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476334/ https://www.ncbi.nlm.nih.gov/pubmed/36116513 http://dx.doi.org/10.1016/j.cbi.2022.110161 |
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