Molecular Docking Studies of Curcumin Analogues against SARS-CoV-2 Spike Protein
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.21577/0103-5053.20210085 http://hdl.handle.net/11449/229556 |
Resumo: | Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the etiologic agent of the current pandemic of coronavirus disease 2019 (COVID-19) that has inflicted the loss of thousands of lives worldwide. The coronavirus surface spike (S) glycoprotein is a class I fusion with a S1 domain which is attached to the human angiotensin converting enzyme 2 (ACE2) receptor, and a S2 domain which enables fusion with the host cell membrane and internalization of the virus. Curcumin has been suggested as a potential drug to control inflammation and as a potential inhibitor of S protein, but its therapeutic effects are hampered by poor bioavailability. We performed a molecular docking and dynamic study using 94 curcumin analogues designed to have improved metabolic stability against the SARS-CoV-2 spike protein and compared their affinity with curcumin and other potential inhibitors. The docking analysis suggested that the S2 domain is the main target of these compounds and compound 2606 displayed a higher binding affinity (-9.6 kcal mol-1) than curcumin (-6.8 kcal mol-1) and the Food and Drug Administration (FDA) approved drug hydroxychloroquine (-6.3 kcal mol-1). Further additional validation in vitro and in vivo of these compounds against SARS-CoV-2 may provide insights into the development of a drug that prevents virus entry into host cells. |
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Molecular Docking Studies of Curcumin Analogues against SARS-CoV-2 Spike ProteinCoronavirusCOVID-19CurcuminMolecular dockingSARSSevere acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the etiologic agent of the current pandemic of coronavirus disease 2019 (COVID-19) that has inflicted the loss of thousands of lives worldwide. The coronavirus surface spike (S) glycoprotein is a class I fusion with a S1 domain which is attached to the human angiotensin converting enzyme 2 (ACE2) receptor, and a S2 domain which enables fusion with the host cell membrane and internalization of the virus. Curcumin has been suggested as a potential drug to control inflammation and as a potential inhibitor of S protein, but its therapeutic effects are hampered by poor bioavailability. We performed a molecular docking and dynamic study using 94 curcumin analogues designed to have improved metabolic stability against the SARS-CoV-2 spike protein and compared their affinity with curcumin and other potential inhibitors. The docking analysis suggested that the S2 domain is the main target of these compounds and compound 2606 displayed a higher binding affinity (-9.6 kcal mol-1) than curcumin (-6.8 kcal mol-1) and the Food and Drug Administration (FDA) approved drug hydroxychloroquine (-6.3 kcal mol-1). Further additional validation in vitro and in vivo of these compounds against SARS-CoV-2 may provide insights into the development of a drug that prevents virus entry into host cells.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)aUnidade de Biotecnologia Universidade de Ribeirão PretoInstituto Federal de Educação Ciência e Tecnologia do Sul de Minas (IFSULDEMINAS)College of Pharmacy and Nutrition University of Saskatchewan, 110 Science PlaceCentro Multiusuário de Inovação Biomolecular (CMIB) Instituto de Biociências Letras e Ciências Exatas Universidade Estadual Paulista (Unesp)Departamento de Física Instituto de Biociências Letras e Ciências Exatas Universidade Estadual Paulista (Unesp)Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas Instituto de Bioquímica Médica Leopoldo de Meis (IBqM) e Centro Nacional de Biologia Estrutural e Bioimagem (CENABIO) Universidade Federal do Rio de Janeiro (UFRJ)gCurso de Medicina Universidade de Ribeirão PretoCurso de Ciências Farmacêuticas Universidade de Ribeirão PretoCentro Multiusuário de Inovação Biomolecular (CMIB) Instituto de Biociências Letras e Ciências Exatas Universidade Estadual Paulista (Unesp)Departamento de Física Instituto de Biociências Letras e Ciências Exatas Universidade Estadual Paulista (Unesp)FAPESP: 18/50008-1FAPESP: 19/03074-1Universidade de Ribeirão PretoCiência e Tecnologia do Sul de Minas (IFSULDEMINAS)University of SaskatchewanUniversidade Estadual Paulista (UNESP)Universidade Federal do Rio de Janeiro (UFRJ)Nogueira, Jéssica R.Verza, Flávia A.Nishimura, FelipeDas, UmashankarCaruso, Ícaro P. [UNESP]Fachin, Ana L.Dimmock, Jonathan R.Marins, Mozart2022-04-29T08:33:12Z2022-04-29T08:33:12Z2021-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1943-1955http://dx.doi.org/10.21577/0103-5053.20210085Journal of the Brazilian Chemical Society, v. 32, n. 10, p. 1943-1955, 2021.1678-47900103-5053http://hdl.handle.net/11449/22955610.21577/0103-5053.202100852-s2.0-85115330048Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of the Brazilian Chemical Societyinfo:eu-repo/semantics/openAccess2022-04-29T08:33:12Zoai:repositorio.unesp.br:11449/229556Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T17:03:32.740359Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Molecular Docking Studies of Curcumin Analogues against SARS-CoV-2 Spike Protein |
title |
Molecular Docking Studies of Curcumin Analogues against SARS-CoV-2 Spike Protein |
spellingShingle |
Molecular Docking Studies of Curcumin Analogues against SARS-CoV-2 Spike Protein Nogueira, Jéssica R. Coronavirus COVID-19 Curcumin Molecular docking SARS |
title_short |
Molecular Docking Studies of Curcumin Analogues against SARS-CoV-2 Spike Protein |
title_full |
Molecular Docking Studies of Curcumin Analogues against SARS-CoV-2 Spike Protein |
title_fullStr |
Molecular Docking Studies of Curcumin Analogues against SARS-CoV-2 Spike Protein |
title_full_unstemmed |
Molecular Docking Studies of Curcumin Analogues against SARS-CoV-2 Spike Protein |
title_sort |
Molecular Docking Studies of Curcumin Analogues against SARS-CoV-2 Spike Protein |
author |
Nogueira, Jéssica R. |
author_facet |
Nogueira, Jéssica R. Verza, Flávia A. Nishimura, Felipe Das, Umashankar Caruso, Ícaro P. [UNESP] Fachin, Ana L. Dimmock, Jonathan R. Marins, Mozart |
author_role |
author |
author2 |
Verza, Flávia A. Nishimura, Felipe Das, Umashankar Caruso, Ícaro P. [UNESP] Fachin, Ana L. Dimmock, Jonathan R. Marins, Mozart |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de Ribeirão Preto Ciência e Tecnologia do Sul de Minas (IFSULDEMINAS) University of Saskatchewan Universidade Estadual Paulista (UNESP) Universidade Federal do Rio de Janeiro (UFRJ) |
dc.contributor.author.fl_str_mv |
Nogueira, Jéssica R. Verza, Flávia A. Nishimura, Felipe Das, Umashankar Caruso, Ícaro P. [UNESP] Fachin, Ana L. Dimmock, Jonathan R. Marins, Mozart |
dc.subject.por.fl_str_mv |
Coronavirus COVID-19 Curcumin Molecular docking SARS |
topic |
Coronavirus COVID-19 Curcumin Molecular docking SARS |
description |
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the etiologic agent of the current pandemic of coronavirus disease 2019 (COVID-19) that has inflicted the loss of thousands of lives worldwide. The coronavirus surface spike (S) glycoprotein is a class I fusion with a S1 domain which is attached to the human angiotensin converting enzyme 2 (ACE2) receptor, and a S2 domain which enables fusion with the host cell membrane and internalization of the virus. Curcumin has been suggested as a potential drug to control inflammation and as a potential inhibitor of S protein, but its therapeutic effects are hampered by poor bioavailability. We performed a molecular docking and dynamic study using 94 curcumin analogues designed to have improved metabolic stability against the SARS-CoV-2 spike protein and compared their affinity with curcumin and other potential inhibitors. The docking analysis suggested that the S2 domain is the main target of these compounds and compound 2606 displayed a higher binding affinity (-9.6 kcal mol-1) than curcumin (-6.8 kcal mol-1) and the Food and Drug Administration (FDA) approved drug hydroxychloroquine (-6.3 kcal mol-1). Further additional validation in vitro and in vivo of these compounds against SARS-CoV-2 may provide insights into the development of a drug that prevents virus entry into host cells. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-01-01 2022-04-29T08:33:12Z 2022-04-29T08:33:12Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.21577/0103-5053.20210085 Journal of the Brazilian Chemical Society, v. 32, n. 10, p. 1943-1955, 2021. 1678-4790 0103-5053 http://hdl.handle.net/11449/229556 10.21577/0103-5053.20210085 2-s2.0-85115330048 |
url |
http://dx.doi.org/10.21577/0103-5053.20210085 http://hdl.handle.net/11449/229556 |
identifier_str_mv |
Journal of the Brazilian Chemical Society, v. 32, n. 10, p. 1943-1955, 2021. 1678-4790 0103-5053 10.21577/0103-5053.20210085 2-s2.0-85115330048 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of the Brazilian Chemical Society |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1943-1955 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808128747699699712 |