Zika Virus Replicons for Drug Discovery

EBioMedicine. 2016 Oct:12:156-160. doi: 10.1016/j.ebiom.2016.09.013. Epub 2016 Sep 14.

Abstract

The current epidemic of Zika virus (ZIKV) has underscored the urgency to establish experimental systems for studying viral replication and pathogenesis, and countermeasure development. Here we report two ZIKV replicon systems: a luciferase replicon that can differentiate between viral translation and RNA synthesis; and a stable luciferase replicon carrying cell line that can be used to screen and characterize inhibitors of viral replication. The transient replicon was used to evaluate the effect of an NS5 polymerase mutation on viral RNA synthesis and to analyze a known ZIKV inhibitor. The replicon cell line was developed into a 96-well format for antiviral testing. Compare with virus infection-based assay, the replicon cell line allows antiviral screening without using infectious virus. Collectively, the replicon systems have provided critical tools for both basic and translational research.

Keywords: Drug discovery; Flavivirus; Replicon; Zika.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Cell Culture Techniques
  • Cell Line
  • Drug Discovery* / methods
  • Drug Evaluation, Preclinical / methods
  • Gene Expression
  • Genes, Reporter
  • Genome, Viral
  • Humans
  • Replicon*
  • Virus Replication / drug effects*
  • Zika Virus / drug effects*
  • Zika Virus / physiology*
  • Zika Virus Infection / drug therapy
  • Zika Virus Infection / virology

Substances

  • Antiviral Agents