The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks zika virus replication
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| 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/22836 |
Resumo: | Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Virologia. Recife, PE, Brasil. |
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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. |
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2017 |
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2017-10-17T11:28:29Z |
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2017-10-17T11:28:29Z |
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2017 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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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. |
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https://www.arca.fiocruz.br/handle/icict/22836 |
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10.1016/j.ijantimicag.2017.08.016 |
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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 |
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