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Antiviral Res ; 180: 104855, 2020 08.
Article in English | MEDLINE | ID: mdl-32574688

ABSTRACT

Zika virus (ZIKV) has gained a lot of attention in the past few years due to its rapid spread worldwide and its close association to severe neurological outcomes, such as microcephaly and Guillain-Barre syndrome. In this study, the in vitro and in vivo anti-ZIKV activity of 7-deaza-7-fluoro-2'-C-methyl-adenosine (DFMA) was evaluated. In vitro, using primary mouse neuronal cells and human neural stem cells infected by ZIKV, treatment with DFMA resulted in impaired viral replication and protection against virus-induced cell death. In vivo, when administrated prior to infection, DFMA prevented lethality and markedly reduced viral loads and neuroinflammation, including microgliosis and overall brain damage. Additionally, as an early therapeutic treatment, DFMA increased survival rates in mice. Collectively, these findings demonstrate that the nucleoside analog DFMA inhibits ZIKV infection and viral-induced neuroinflammation in vitro and in vivo without apparent untoward effects, suggesting it may be useful in individuals infected with ZIKV.


Subject(s)
Adenosine/analogs & derivatives , Antiviral Agents/pharmacology , Inflammation/virology , Nervous System Diseases/virology , Zika Virus Infection/complications , Adenosine/pharmacology , Adenosine/therapeutic use , Animals , Antiviral Agents/therapeutic use , Cell Line , Cells, Cultured , Chlorocebus aethiops , Culicidae/cytology , Humans , Inflammation/drug therapy , Mice , Nervous System Diseases/drug therapy , Neural Stem Cells , Vero Cells , Viral Load/drug effects , Virus Replication/drug effects , Zika Virus , Zika Virus Infection/drug therapy
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