Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19

Bibliographic Details
Main Author: de Andrade Neto, João Batista
Publication Date: 2022
Other Authors: 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
Format: Article
Language: por
Source: Journal of Health & Biological Sciences
Download full: https://periodicos.unichristus.edu.br/jhbs/article/view/4238
Summary: 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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spelling 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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