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Antiviral Res. 2017 Mar;139:117-128. doi: 10.1016/j.antiviral.2016.12.022. Epub 2016 Dec 31.

Obatoclax, saliphenylhalamide and gemcitabine inhibit Zika virus infection in vitro and differentially affect cellular signaling, transcription and metabolism.

Author information

1
Department of Virology, Medicum, University of Helsinki, Finland.
2
Department of Molecular Neurology, Biomedicum Stem Cells Center Research Program Unit, University of Helsinki, Finland.
3
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Finland.
4
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, USA; Department of Virology and Immunology, University of Helsinki and Helsinki University Hospital, Finland.
5
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Finland. Electronic address: denis.kainov@helsinki.fi.
6
Department of Virology, Medicum, University of Helsinki, Finland; Department of Virology and Immunology, University of Helsinki and Helsinki University Hospital, Finland; Department of Veterinary Biosciences, University of Helsinki, Finland. Electronic address: olli.vapalahti@helsinki.fi.

Abstract

An epidemic of Zika virus (ZIKV) infection associated with congenital abnormalities such as microcephaly, is ongoing in the Americas and the Pacific. Currently there are no approved therapies to treat this emerging viral disease. Here, we tested three cell-directed broad-spectrum antiviral compounds against ZIKV replication using human retinal pigment epithelial (RPE) cells and a low-passage ZIKV strain isolated from fetal brain. We found that obatoclax, SaliPhe, and gemcitabine inhibited ZIKV infections at noncytotoxic concentrations. Moreover, all three compounds prevented production of viral RNA and proteins as well as activation of cellular caspase 8, 3 and 7. However, these compounds differentially affected ZIKV-mediated transcription, translation and posttranslational modifications of cellular factors as well as metabolic pathways indicating that these agents possess different mechanisms of action. Interestingly, combination of obatoclax and SaliPhe at nanomolar concentrations had a synergistic effect against ZIKV infection. Thus, our results provided the foundation for development of broad-spectrum cell-directed antivirals or their combinations for treatment of ZIKV and other emerging viral diseases.

PMID:
28049006
DOI:
10.1016/j.antiviral.2016.12.022
[Indexed for MEDLINE]

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