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

Suvi Kuivanen, Maxim M. Bespalov, Jatin Nandania, Aleksandr Ianevski, Vidya Velagapudi, Jef K. De Brabander, Denis E. Kainov, Olli Vapalahti

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)117-128
Number of pages12
JournalAntiviral Research
Volume139
DOIs
StatePublished - Mar 1 2017

Fingerprint

gemcitabine
Virus Diseases
Antiviral Agents
Caspase 7
Virus Activation
Microcephaly
Retinal Pigments
Caspase 8
Viral RNA
Viral Proteins
Post Translational Protein Processing
Virus Replication
Metabolic Networks and Pathways
Caspase 3
Epithelial Cells
Zika Virus Infection
saliphenylhalamide
obatoclax
Zika Virus
Brain

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Cite this

Obatoclax, saliphenylhalamide and gemcitabine inhibit Zika virus infection in vitro and differentially affect cellular signaling, transcription and metabolism. / Kuivanen, Suvi; Bespalov, Maxim M.; Nandania, Jatin; Ianevski, Aleksandr; Velagapudi, Vidya; De Brabander, Jef K.; Kainov, Denis E.; Vapalahti, Olli.

In: Antiviral Research, Vol. 139, 01.03.2017, p. 117-128.

Research output: Contribution to journalArticle

Kuivanen, Suvi ; Bespalov, Maxim M. ; Nandania, Jatin ; Ianevski, Aleksandr ; Velagapudi, Vidya ; De Brabander, Jef K. ; Kainov, Denis E. ; Vapalahti, Olli. / Obatoclax, saliphenylhalamide and gemcitabine inhibit Zika virus infection in vitro and differentially affect cellular signaling, transcription and metabolism. In: Antiviral Research. 2017 ; Vol. 139. pp. 117-128.
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