7-Deaza-7-fluoro-2'-C-methyladenosine inhibits Zika virus infection and viral-induced neuroinflammation.

Autor: Del Sarto JL; Department of Biochemistry and Immunology, And(2)Research Center for Drug Development, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Rocha RPF; Department of Biochemistry and Immunology, And(2)Research Center for Drug Development, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Bassit L; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA., Olmo IG; Neurobiochemistry Laboratory, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil., Valiate B; Department of Biochemistry and Immunology, And(2)Research Center for Drug Development, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Queiroz-Junior CM; Cardiac Biology Laboratory, Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., Pedrosa CDSG; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Ribeiro FM; Neurobiochemistry Laboratory, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil., Guimarães MZ; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Rehen S; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Amblard F; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA., Zhou L; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA., Cox BD; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA., Gavegnano C; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA., Costa VV; Department of Biochemistry and Immunology, And(2)Research Center for Drug Development, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Research Group in Arboviral Diseases. Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil., Schinazi RF; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA. Electronic address: rschina@emory.edu., Teixeira MM; Department of Biochemistry and Immunology, And(2)Research Center for Drug Development, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: mmtex@icb.ufmg.br.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2020 Aug; Vol. 180, pp. 104855. Date of Electronic Publication: 2020 Jun 20.
DOI: 10.1016/j.antiviral.2020.104855
Abstrakt: 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.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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