The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks Zika virus replication
| Autor: | Lindomar Pena, Marli Tenório Cordeiro, Daniele Mendes Félix, Catarina Maria Cataldi Sabino de Araújo, Rafael F. O. França, Leila R de Mendonça, Abelardo Silva Júnior, Otávio Valério de Carvalho |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Cell Survival 030106 microbiology Azathioprine Methylthioinosine Virus Replication Antiviral Agents Virus Zika virus Cell Line 03 medical and health sciences In vivo medicine Cytotoxic T cell Animals Humans Pharmacology (medical) Cytotoxicity Neurons biology Zika Virus Infection Epithelial Cells General Medicine Zika Virus biology.organism_classification Virology 030104 developmental biology Infectious Diseases Cell culture Vero cell Brazil medicine.drug |
| Zdroj: | International journal of antimicrobial agents. 50(6) |
| ISSN: | 1872-7913 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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