The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks zika virus replication

Detalhes bibliográficos
Autor(a) principal: Carvalho, Otavio Valério de
Data de Publicação: 2017
Outros Autores: Félix, Daniele Mendes, Mendonça, Leila Rodrigues de, Araújo, Catarina Maria Cataldi Sabino de, Franca, Rafael Freitas de Oliveira, Cordeiro, Marli Tenório, Júnior, Abelardo Silva, Pena, Lindomar José
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/22836
Resumo: Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Virologia. Recife, PE, Brasil.
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spelling Carvalho, Otavio Valério deFélix, Daniele MendesMendonça, Leila Rodrigues deAraújo, Catarina Maria Cataldi Sabino deFranca, Rafael Freitas de OliveiraCordeiro, Marli TenórioJúnior, Abelardo SilvaPena, Lindomar José2017-10-17T11:28:29Z2017-10-17T11:28:29Z2017CARVALHO, Otavio Valério de et al. The Thiopurine Nucleoside Analogue 6-0Methylmercaptopurine Riboside (6MMPr) Effectively Blocks Zika Virus Replication. International Journal of Antimicrobial Agents, p. 1-19, Aug. 2017.https://www.arca.fiocruz.br/handle/icict/2283610.1016/j.ijantimicag.2017.08.016engElsevierThe thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks zika virus replicationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Virologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Virologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Virologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Virologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Virologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Virologia. Recife, PE, Brasil.Universidade Federal de Viçosa. Departamento de Medicina Veterinária. Viçosa, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Virologia. Recife, PE, Brasil.Since the emergence of Zika virus (ZIKV) in Brazil in 2015, 48 countries and territories in the Americas have confirmed autochthonous cases of the disease caused by the virus. The ZIKV-associated neurological manifestations and congenital defects make the development of safe and effective antivirals against ZIKV of utmost importance. Here, we evaluated the antiviral activity of 6-methylmercaptopurine riboside (6MMPr), a thiopurine nucleoside analog derived from the prodrug azathioprine (AZA), against the epidemic ZIKV strain circulating in Brazil. In all the assays, an epithelial (Vero) and an human neuronal (SH-SY5Y) cell line were used to evaluate the cytotoxicity and the effective concentrations of 6MMPr against ZIKV. The levels of ZIKV RNA, viral infectious titer and the percentage of infected cells at the presence or absence of 6MMPr was used to determine the antiviral efficacy. We show that 6MMPr decreased ZIKV production by more than 99% in both cell lines in a dose- and time-dependent way. Interestingly, 6MMPr was 1.6 times less toxic to SH-SY5Y cells compared to Vero cells, presenting a 50% cytotoxic concentration (CC50) of 460.3 µM and 291 µM, respectively. The selectivity index of 6MMPr for Vero and SH-SY5Y cells was 11.9 and 22.7, respectively, highlighting the safety profile of the drug to neuronal cells. Taken together, our results identify, for the first time, the thiopurine nucleoside analog 6MMPr as promising antiviral candidate against ZIKV that warrants further in vivo evaluation.AntiviralZika virusCytotoxicity6MMPrVeroNeuronal CellsNãoNão Publicadoinfo: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/22836/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALdaniele_felix_etal_IOC_2017.pdfdaniele_felix_etal_IOC_2017.pdfapplication/pdf876548https://www.arca.fiocruz.br/bitstream/icict/22836/2/daniele_felix_etal_IOC_2017.pdfdced0c5bb1b2d70bd448898cb4864877MD52TEXTdaniele_felix_etal_IOC_2017.pdf.txtdaniele_felix_etal_IOC_2017.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks zika virus replication
title The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks zika virus replication
spellingShingle The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks zika virus replication
Carvalho, Otavio Valério de
Antiviral
Zika virus
Cytotoxicity
6MMPr
Vero
Neuronal Cells
title_short The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks zika virus replication
title_full The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks zika virus replication
title_fullStr The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks zika virus replication
title_full_unstemmed The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks zika virus replication
title_sort The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks zika virus replication
author Carvalho, Otavio Valério de
author_facet Carvalho, Otavio Valério de
Félix, Daniele Mendes
Mendonça, Leila Rodrigues de
Araújo, Catarina Maria Cataldi Sabino de
Franca, Rafael Freitas de Oliveira
Cordeiro, Marli Tenório
Júnior, Abelardo Silva
Pena, Lindomar José
author_role author
author2 Félix, Daniele Mendes
Mendonça, Leila Rodrigues de
Araújo, Catarina Maria Cataldi Sabino de
Franca, Rafael Freitas de Oliveira
Cordeiro, Marli Tenório
Júnior, Abelardo Silva
Pena, Lindomar José
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Carvalho, Otavio Valério de
Félix, Daniele Mendes
Mendonça, Leila Rodrigues de
Araújo, Catarina Maria Cataldi Sabino de
Franca, Rafael Freitas de Oliveira
Cordeiro, Marli Tenório
Júnior, Abelardo Silva
Pena, Lindomar José
dc.subject.en.pt_BR.fl_str_mv Antiviral
Zika virus
Cytotoxicity
6MMPr
Vero
Neuronal Cells
topic Antiviral
Zika virus
Cytotoxicity
6MMPr
Vero
Neuronal Cells
description Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Virologia. Recife, PE, Brasil.
publishDate 2017
dc.date.accessioned.fl_str_mv 2017-10-17T11:28:29Z
dc.date.available.fl_str_mv 2017-10-17T11:28:29Z
dc.date.issued.fl_str_mv 2017
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 CARVALHO, Otavio Valério de et al. The Thiopurine Nucleoside Analogue 6-0Methylmercaptopurine Riboside (6MMPr) Effectively Blocks Zika Virus Replication. International Journal of Antimicrobial Agents, p. 1-19, Aug. 2017.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/22836
dc.identifier.doi.pt_BR.fl_str_mv 10.1016/j.ijantimicag.2017.08.016
identifier_str_mv CARVALHO, Otavio Valério de et al. The Thiopurine Nucleoside Analogue 6-0Methylmercaptopurine Riboside (6MMPr) Effectively Blocks Zika Virus Replication. International Journal of Antimicrobial Agents, p. 1-19, Aug. 2017.
10.1016/j.ijantimicag.2017.08.016
url https://www.arca.fiocruz.br/handle/icict/22836
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 Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
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instname_str Fundação Oswaldo Cruz (FIOCRUZ)
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