SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites

Detalhes bibliográficos
Autor(a) principal: Lechuga, Guilherme Curty
Data de Publicação: 2021
Outros Autores: 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
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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spelling 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
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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https://www.arca.fiocruz.br/bitstream/icict/48984/2/GuilhermeLechuga_SalvatoreSiciliano_etal_IOC_2021.pdf
https://www.arca.fiocruz.br/bitstream/icict/48984/3/GuilhermeLechuga_SalvatoreSiciliano_etal_IOC_2021.pdf.txt
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