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

45 Scopus citations

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

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Fingerprint Dive into the research topics of 'Obatoclax, saliphenylhalamide and gemcitabine inhibit Zika virus infection in vitro and differentially affect cellular signaling, transcription and metabolism'. Together they form a unique fingerprint.

  • Cite this