Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Journal of Health & Biological Sciences |
Texto Completo: | https://periodicos.unichristus.edu.br/jhbs/article/view/4238 |
Resumo: | INTRODUCTION: COVID-19 has quickly become one of the main pathogens of the human respiratory tract and poses a great threat to public health. The high number of cases has caused the World Health Organization to declare a global state of emergency. In addition, due to the limited number of therapeutic strategies, high levels of mortality have been observed in several regions of the world. Within this context, repositioning of drugs based on lysosomotropic and endolysosomal pH modulating effects can provide additional options for therapy and prevention of the new disease. METHODS: Molecular docking analyses of these lysosomotropic agents were performed, namely of fluoxetine, imipramine, chloroquine, verapamil, tamoxifen, amitriptyline and chlorpromazine against important targets for the pathogenesis of SARS-CoV-2. RESULTS: The results revealed that the inhibitors bind to distinct regions of Mpro COVID-19, with variations in RMSD values from 1.325 to 1.962 Å and a binding free energy of -5.2 to -4.3 kcal/mol. Furthermore, the analysis of the second target showed that all inhibitors bonded at the same site as the enzyme and the interaction resulted in an RMSD variation of 0.735 to 1.562 Å and binding free energy ranging from -6.0 to -8.7 kcal/mol. CONCLUSION: Therefore, this study allows proposing the use of these lysosomotropic compounds. However, these computer simulations are just an initial step toward conceiving new projects for the development of antiviral molecules. Keywords: COVID-19; Inhibitors; lysossomotropics; molecular docking |
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Journal of Health & Biological Sciences |
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Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19Lysosomotropic agents; SARS-CoV; Molecular DockingINTRODUCTION: COVID-19 has quickly become one of the main pathogens of the human respiratory tract and poses a great threat to public health. The high number of cases has caused the World Health Organization to declare a global state of emergency. In addition, due to the limited number of therapeutic strategies, high levels of mortality have been observed in several regions of the world. Within this context, repositioning of drugs based on lysosomotropic and endolysosomal pH modulating effects can provide additional options for therapy and prevention of the new disease. METHODS: Molecular docking analyses of these lysosomotropic agents were performed, namely of fluoxetine, imipramine, chloroquine, verapamil, tamoxifen, amitriptyline and chlorpromazine against important targets for the pathogenesis of SARS-CoV-2. RESULTS: The results revealed that the inhibitors bind to distinct regions of Mpro COVID-19, with variations in RMSD values from 1.325 to 1.962 Å and a binding free energy of -5.2 to -4.3 kcal/mol. Furthermore, the analysis of the second target showed that all inhibitors bonded at the same site as the enzyme and the interaction resulted in an RMSD variation of 0.735 to 1.562 Å and binding free energy ranging from -6.0 to -8.7 kcal/mol. CONCLUSION: Therefore, this study allows proposing the use of these lysosomotropic compounds. However, these computer simulations are just an initial step toward conceiving new projects for the development of antiviral molecules. Keywords: COVID-19; Inhibitors; lysossomotropics; molecular dockingObjective: Analyze lysosomotropic agents and their action on COVID-19 targets using the molecular docking technique. Methods: Molecular docking analyses of these lysosomotropic agents were performed, namely of fluoxetine, imipramine, chloroquine, verapamil, tamoxifen, amitriptyline, and chlorpromazine against important targets for the pathogenesis of SARS-CoV-2. Results: The results revealed that the inhibitors bind to distinct regions of Mpro COVID-19, with variations in RMSD values from 1.325 to 1.962 Å and binding free energy of -5.2 to -4.3 kcal/mol. Furthermore, the analysis of the second target showed that all inhibitors bonded at the same site as the enzyme, and the interaction resulted in an RMSD variation of 0.735 to 1.562 Å and binding free energy ranging from -6.0 to -8.7 kcal/mol. Conclusion: Therefore, this study allows proposing the use of these lysosomotropic compounds. However, these computer simulations are just an initial step toward conceiving new projects for the development of antiviral molecules.Instituto para o Desenvolvimento da Educacaode Andrade Neto, João BatistaMarinho, Emanuelle Machadoda Silva, Cecília RochaValente Sá, Lívia Gurgel do AmaralCabral, Vitória Pessoa de FariasCândido, Thiago MesquitaBarbosa da Silva, Wildson MaxBarbosa, Letícia BernardoCavalcanti, Bruno CoelhoNeto, Pedro de LimaMarinho, Emmanuel SilvaCardoso Viana Gomes, Akenaton OnassisNobre Júnior, Hélio Vitoriano2022-06-30info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAvaliado por ParesPeer ReviewRevisado por paresapplication/pdfhttps://periodicos.unichristus.edu.br/jhbs/article/view/423810.12662/2317-3076jhbs.v10i1.4238.p1-12.2022Journal of Health & Biological Sciences; v. 10, n. 1 (2022): Journal of Health and Biological Sciences; 1-12Journal of Health & Biological Sciences; v. 10, n. 1 (2022): Journal of Health and Biological Sciences; 1-12Journal of Health and Biological Sciences; v. 10, n. 1 (2022): Journal of Health and Biological Sciences; 1-122317-30762317-308410.12662/2317-3076jhbs.v10i1.2022reponame:Journal of Health & Biological Sciencesinstname:Centro Universitário Christus (Unichristus)instacron:CHRISTUSporhttps://periodicos.unichristus.edu.br/jhbs/article/view/4238/1605https://periodicos.unichristus.edu.br/jhbs/article/downloadSuppFile/4238/1276Direitos autorais 2022 Journal of Health & Biological Scienceshttp://creativecommons.org/licenses/by-nc-sa/4.0info:eu-repo/semantics/openAccess2022-12-31T20:14:06Zoai:ojs.unichristus.emnuvens.com.br:article/4238Revistahttps://periodicos.unichristus.edu.br/jhbs/indexPRIhttps://periodicos.unichristus.edu.br/jhbs/oaisecretaria.jhbs@unichristus.edu.br || editor.jhbs@fchristus.edu.br2317-30762317-3084opendoar:2023-01-13T09:47:13.417235Journal of Health & Biological Sciences - Centro Universitário Christus (Unichristus)true |
dc.title.none.fl_str_mv |
Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19 Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19 |
title |
Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19 |
spellingShingle |
Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19 de Andrade Neto, João Batista Lysosomotropic agents; SARS-CoV; Molecular Docking |
title_short |
Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19 |
title_full |
Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19 |
title_fullStr |
Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19 |
title_full_unstemmed |
Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19 |
title_sort |
Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19 |
author |
de Andrade Neto, João Batista |
author_facet |
de Andrade Neto, João Batista Marinho, Emanuelle Machado da Silva, Cecília Rocha Valente Sá, Lívia Gurgel do Amaral Cabral, Vitória Pessoa de Farias Cândido, Thiago Mesquita Barbosa da Silva, Wildson Max Barbosa, Letícia Bernardo Cavalcanti, Bruno Coelho Neto, Pedro de Lima Marinho, Emmanuel Silva Cardoso Viana Gomes, Akenaton Onassis Nobre Júnior, Hélio Vitoriano |
author_role |
author |
author2 |
Marinho, Emanuelle Machado da Silva, Cecília Rocha Valente Sá, Lívia Gurgel do Amaral Cabral, Vitória Pessoa de Farias Cândido, Thiago Mesquita Barbosa da Silva, Wildson Max Barbosa, Letícia Bernardo Cavalcanti, Bruno Coelho Neto, Pedro de Lima Marinho, Emmanuel Silva Cardoso Viana Gomes, Akenaton Onassis Nobre Júnior, Hélio Vitoriano |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
|
dc.contributor.author.fl_str_mv |
de Andrade Neto, João Batista Marinho, Emanuelle Machado da Silva, Cecília Rocha Valente Sá, Lívia Gurgel do Amaral Cabral, Vitória Pessoa de Farias Cândido, Thiago Mesquita Barbosa da Silva, Wildson Max Barbosa, Letícia Bernardo Cavalcanti, Bruno Coelho Neto, Pedro de Lima Marinho, Emmanuel Silva Cardoso Viana Gomes, Akenaton Onassis Nobre Júnior, Hélio Vitoriano |
dc.subject.none.fl_str_mv |
|
dc.subject.por.fl_str_mv |
Lysosomotropic agents; SARS-CoV; Molecular Docking |
topic |
Lysosomotropic agents; SARS-CoV; Molecular Docking |
description |
INTRODUCTION: COVID-19 has quickly become one of the main pathogens of the human respiratory tract and poses a great threat to public health. The high number of cases has caused the World Health Organization to declare a global state of emergency. In addition, due to the limited number of therapeutic strategies, high levels of mortality have been observed in several regions of the world. Within this context, repositioning of drugs based on lysosomotropic and endolysosomal pH modulating effects can provide additional options for therapy and prevention of the new disease. METHODS: Molecular docking analyses of these lysosomotropic agents were performed, namely of fluoxetine, imipramine, chloroquine, verapamil, tamoxifen, amitriptyline and chlorpromazine against important targets for the pathogenesis of SARS-CoV-2. RESULTS: The results revealed that the inhibitors bind to distinct regions of Mpro COVID-19, with variations in RMSD values from 1.325 to 1.962 Å and a binding free energy of -5.2 to -4.3 kcal/mol. Furthermore, the analysis of the second target showed that all inhibitors bonded at the same site as the enzyme and the interaction resulted in an RMSD variation of 0.735 to 1.562 Å and binding free energy ranging from -6.0 to -8.7 kcal/mol. CONCLUSION: Therefore, this study allows proposing the use of these lysosomotropic compounds. However, these computer simulations are just an initial step toward conceiving new projects for the development of antiviral molecules. Keywords: COVID-19; Inhibitors; lysossomotropics; molecular docking |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-06-30 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Avaliado por Pares Peer Review Revisado por pares |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://periodicos.unichristus.edu.br/jhbs/article/view/4238 10.12662/2317-3076jhbs.v10i1.4238.p1-12.2022 |
url |
https://periodicos.unichristus.edu.br/jhbs/article/view/4238 |
identifier_str_mv |
10.12662/2317-3076jhbs.v10i1.4238.p1-12.2022 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
https://periodicos.unichristus.edu.br/jhbs/article/view/4238/1605 https://periodicos.unichristus.edu.br/jhbs/article/downloadSuppFile/4238/1276 |
dc.rights.driver.fl_str_mv |
Direitos autorais 2022 Journal of Health & Biological Sciences http://creativecommons.org/licenses/by-nc-sa/4.0 info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Direitos autorais 2022 Journal of Health & Biological Sciences http://creativecommons.org/licenses/by-nc-sa/4.0 |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.coverage.none.fl_str_mv |
|
dc.publisher.none.fl_str_mv |
Instituto para o Desenvolvimento da Educacao |
publisher.none.fl_str_mv |
Instituto para o Desenvolvimento da Educacao |
dc.source.none.fl_str_mv |
Journal of Health & Biological Sciences; v. 10, n. 1 (2022): Journal of Health and Biological Sciences; 1-12 Journal of Health & Biological Sciences; v. 10, n. 1 (2022): Journal of Health and Biological Sciences; 1-12 Journal of Health and Biological Sciences; v. 10, n. 1 (2022): Journal of Health and Biological Sciences; 1-12 2317-3076 2317-3084 10.12662/2317-3076jhbs.v10i1.2022 reponame:Journal of Health & Biological Sciences instname:Centro Universitário Christus (Unichristus) instacron:CHRISTUS |
instname_str |
Centro Universitário Christus (Unichristus) |
instacron_str |
CHRISTUS |
institution |
CHRISTUS |
reponame_str |
Journal of Health & Biological Sciences |
collection |
Journal of Health & Biological Sciences |
repository.name.fl_str_mv |
Journal of Health & Biological Sciences - Centro Universitário Christus (Unichristus) |
repository.mail.fl_str_mv |
secretaria.jhbs@unichristus.edu.br || editor.jhbs@fchristus.edu.br |
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1797052855341809664 |