SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites
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 FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/48984 |
Resumo: | Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil. |
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Lechuga, Guilherme CurtySilva, Franklin SouzaSacramento, Carolina Q.Trugilho, Monique R. O.Valente, Richard H.Pêgo, Paloma NapoleãoDias, Suelen S. G.Rodrigues, Natalia FintelmanTemerozo, Jairo RamosCarels, NicolasAlves, Carlos R.Pereira, Mirian C. S.Provance Junior, David WilliamSouza, Thiago Moreno L.De Simone, Salvatore Giovanni2021-09-05T13:07:53Z2021-09-05T13:07:53Z2021LECHUGA, Guilherme C. et al. SARS-CoV-2 Proteins Bind to Hemoglobin and its Metabolites. International Journal of Molecular Sciences, v. 22, p. 1-20, 2021.1422-0067https://www.arca.fiocruz.br/handle/icict/4898410.3390/ijms22169035engMDPISARS-CoV-2COVID-19Ligação proteína-proteínaHemoglobinaSARS-CoV-2COVID-19Protein–protein bindingHemoglobinHeminRBDNsp3Nsp7SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolitesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Universidade Iguaçu. Faculdade de Biologia e Ciências da Saúde.. Nova Iguaçu, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Insstituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Universidade Iguaçu. Faculdade de Biologia e Ciências da Saúde.. Nova Iguaçu, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Universidade Federal Fluminense. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil.(1) Background: coronavirus disease 2019 (COVID-19), caused by severe acute respira tory syndrome coronavirus 2 (SARS-CoV-2), has been linked to hematological dysfunctions, but there are little experimental data that explain this. Spike (S) and Nucleoprotein (N) proteins have been putatively associated with these dysfunctions. In this work, we analyzed the recruitment of hemoglobin (Hb) and other metabolites (hemin and protoporphyrin IX-PpIX) by SARS-Cov2 proteins using different approaches. (2) Methods: shotgun proteomics (LC–MS/MS) after affinity column adsorption identified hemin-binding SARS-CoV-2 proteins. The parallel synthesis of the peptides technique was used to study the interaction of the receptor bind domain (RBD) and N-terminal domain (NTD) of the S protein with Hb and in silico analysis to identify the binding motifs of the N protein. The plaque assay was used to investigate the inhibitory effect of Hb and the metabolites hemin and PpIX on virus adsorption and replication in Vero cells. (3) Results: the proteomic analysis by LC–MS/MS identified the S, N, M, Nsp3, and Nsp7 as putative hemin-binding proteins. Six short sequences in the RBD and 11 in the NTD of the spike were identified by microarray of peptides to interact with Hb and tree motifs in the N protein by in silico analysis to bind with heme. An inhibitory effect in vitro of Hb, hemin, and PpIX at different levels was observed. Strikingly, free Hb at 1mM suppressed viral replication (99%), and its interaction with SARS-CoV-2 was localized into the RBD region of the spike protein. (4) Conclusions: in this study, we identified that (at least) five proteins (S, N, M, Nsp3, and Nsp7) of SARS-CoV-2 recruit Hb/metabolites. The motifs of the RDB of SARS-CoV-2 spike, which binds Hb, and the sites of the heme bind-N protein were disclosed. In addition, these compounds and PpIX block the virus’s adsorption and replication. Furthermore, we also identified heme-binding motifs and interaction with hemin in N protein and other structural (S and M) and non-structural (Nsp3 and Nsp7) proteins.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/48984/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALGuilhermeLechuga_SalvatoreSiciliano_etal_IOC_2021.pdfGuilhermeLechuga_SalvatoreSiciliano_etal_IOC_2021.pdfapplication/pdf3888491https://www.arca.fiocruz.br/bitstream/icict/48984/2/GuilhermeLechuga_SalvatoreSiciliano_etal_IOC_2021.pdf3819a782e73abbeb87637f94a24d4c9dMD52TEXTGuilhermeLechuga_SalvatoreSiciliano_etal_IOC_2021.pdf.txtGuilhermeLechuga_SalvatoreSiciliano_etal_IOC_2021.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv |
SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites |
title |
SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites |
spellingShingle |
SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites Lechuga, Guilherme Curty SARS-CoV-2 COVID-19 Ligação proteína-proteína Hemoglobina SARS-CoV-2 COVID-19 Protein–protein binding Hemoglobin Hemin RBD Nsp3 Nsp7 |
title_short |
SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites |
title_full |
SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites |
title_fullStr |
SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites |
title_full_unstemmed |
SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites |
title_sort |
SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites |
author |
Lechuga, Guilherme Curty |
author_facet |
Lechuga, Guilherme Curty Silva, Franklin Souza Sacramento, Carolina Q. Trugilho, Monique R. O. Valente, Richard H. Pêgo, Paloma Napoleão Dias, Suelen S. G. Rodrigues, Natalia Fintelman Temerozo, Jairo Ramos Carels, Nicolas Alves, Carlos R. Pereira, Mirian C. S. Provance Junior, David William Souza, Thiago Moreno L. De Simone, Salvatore Giovanni |
author_role |
author |
author2 |
Silva, Franklin Souza Sacramento, Carolina Q. Trugilho, Monique R. O. Valente, Richard H. Pêgo, Paloma Napoleão Dias, Suelen S. G. Rodrigues, Natalia Fintelman Temerozo, Jairo Ramos Carels, Nicolas Alves, Carlos R. Pereira, Mirian C. S. Provance Junior, David William Souza, Thiago Moreno L. De Simone, Salvatore Giovanni |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Lechuga, Guilherme Curty Silva, Franklin Souza Sacramento, Carolina Q. Trugilho, Monique R. O. Valente, Richard H. Pêgo, Paloma Napoleão Dias, Suelen S. G. Rodrigues, Natalia Fintelman Temerozo, Jairo Ramos Carels, Nicolas Alves, Carlos R. Pereira, Mirian C. S. Provance Junior, David William Souza, Thiago Moreno L. De Simone, Salvatore Giovanni |
dc.subject.other.pt_BR.fl_str_mv |
SARS-CoV-2 COVID-19 Ligação proteína-proteína Hemoglobina |
topic |
SARS-CoV-2 COVID-19 Ligação proteína-proteína Hemoglobina SARS-CoV-2 COVID-19 Protein–protein binding Hemoglobin Hemin RBD Nsp3 Nsp7 |
dc.subject.en.pt_BR.fl_str_mv |
SARS-CoV-2 COVID-19 Protein–protein binding Hemoglobin Hemin RBD Nsp3 Nsp7 |
description |
Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-09-05T13:07:53Z |
dc.date.available.fl_str_mv |
2021-09-05T13:07:53Z |
dc.date.issued.fl_str_mv |
2021 |
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.citation.fl_str_mv |
LECHUGA, Guilherme C. et al. SARS-CoV-2 Proteins Bind to Hemoglobin and its Metabolites. International Journal of Molecular Sciences, v. 22, p. 1-20, 2021. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/48984 |
dc.identifier.issn.pt_BR.fl_str_mv |
1422-0067 |
dc.identifier.doi.none.fl_str_mv |
10.3390/ijms22169035 |
identifier_str_mv |
LECHUGA, Guilherme C. et al. SARS-CoV-2 Proteins Bind to Hemoglobin and its Metabolites. International Journal of Molecular Sciences, v. 22, p. 1-20, 2021. 1422-0067 10.3390/ijms22169035 |
url |
https://www.arca.fiocruz.br/handle/icict/48984 |
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eng |
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eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
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reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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FIOCRUZ |
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FIOCRUZ |
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