High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain. Academic Article uri icon

Overview

abstract

  • Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids. Finally, HH and AQ inhibit ZIKV infection in adult mouse brain in vivo. Strikingly, HH suppresses viral propagation when administered to adult mice with active ZIKV infection, highlighting its therapeutic potential. Our approach highlights the power of stem cell-based screens and validation in human forebrain organoids and mouse models in identifying drug candidates for treating ZIKV infection and related neurological complications in fetal and adult patients.

publication date

  • July 20, 2017

Research

keywords

  • Antiviral Agents
  • Brain
  • Drug Evaluation, Preclinical
  • Induced Pluripotent Stem Cells
  • Neural Stem Cells
  • Organoids
  • Zika Virus
  • Zika Virus Infection

Identity

PubMed Central ID

  • PMC5553280

Scopus Document Identifier

  • 85025475900

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2017.06.017

PubMed ID

  • 28736217

Additional Document Info

volume

  • 21

issue

  • 2