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The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks Zika virus replication.
de Carvalho, Otavio Valério; Félix, Daniele Mendes; de Mendonça, Leila Rodrigues; de Araújo, Catarina Maria Cataldi Sabino; de Oliveira Franca, Rafael Freitas; Cordeiro, Marli Tenório; Silva Júnior, Abelardo; Pena, Lindomar José.
Afiliação
  • de Carvalho OV; Department of Virology, Oswaldo Cruz Foundation (Fiocruz), Avenida Professor Moraes Rego, Recife, Pernambuco, Brazil.
  • Félix DM; Department of Virology, Oswaldo Cruz Foundation (Fiocruz), Avenida Professor Moraes Rego, Recife, Pernambuco, Brazil.
  • de Mendonça LR; Department of Virology, Oswaldo Cruz Foundation (Fiocruz), Avenida Professor Moraes Rego, Recife, Pernambuco, Brazil.
  • de Araújo CMCS; Department of Virology, Oswaldo Cruz Foundation (Fiocruz), Avenida Professor Moraes Rego, Recife, Pernambuco, Brazil.
  • de Oliveira Franca RF; Department of Virology, Oswaldo Cruz Foundation (Fiocruz), Avenida Professor Moraes Rego, Recife, Pernambuco, Brazil.
  • Cordeiro MT; Department of Virology, Oswaldo Cruz Foundation (Fiocruz), Avenida Professor Moraes Rego, Recife, Pernambuco, Brazil.
  • Silva Júnior A; Department of Veterinary Medicine, Federal University of Viçosa (UFV), Av. PH Rolfs, s/n, Viçosa, Minas Gerais 36570-900, Brazil. Electronic address: asjvet@gmail.com.
  • Pena LJ; Department of Virology, Oswaldo Cruz Foundation (Fiocruz), Avenida Professor Moraes Rego, Recife, Pernambuco, Brazil. Electronic address: lindomar.pena@cpqam.fiocruz.br.
Int J Antimicrob Agents ; 50(6): 718-725, 2017 Dec.
Article em En | MEDLINE | ID: mdl-28803932
Since the emergence of Zika virus (ZIKV) in Brazil in 2015, 48 countries and territories in the Americas have confirmed autochthonous cases of disease caused by the virus. 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 analogue derived from the prodrug azathioprine, against the epidemic ZIKV strain circulating in Brazil. In all of the assays, an epithelial (Vero) and a human neuronal (SH-SY5Y) cell line were used to evaluate the cytotoxicity and effective concentrations of 6MMPr against ZIKV. Levels of ZIKV-RNA, viral infectious titre and the percentage of infected cells in the presence or absence of 6MMPr were used to determine antiviral efficacy. 6MMPr decreased ZIKV production by >99% in both cell lines in a dose- and time-dependent manner. Interestingly, 6MMPr was 1.6 times less toxic to SH-SY5Y cells compared with Vero cells, presenting a 50% cytotoxic concentrations (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, these results identify, for the first time, the thiopurine nucleoside analogue 6MMPr as a promising antiviral candidate against ZIKV that warrants further in vivo evaluation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Replicação Viral / Zika virus / Metiltioinosina Limite: Animals / Humans País/Região como assunto: America do sul / Brasil Idioma: En Revista: Int J Antimicrob Agents Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Replicação Viral / Zika virus / Metiltioinosina Limite: Animals / Humans País/Região como assunto: America do sul / Brasil Idioma: En Revista: Int J Antimicrob Agents Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda