High-content screening in hPSC-neural progenitors identifies drug candidates that inhibit Zika virus infection in fetal-like organoids and adult brain Journal Article

   

Authors:	Zhou, T.; Tan, L.; Cederquist, G. Y.; Fan, Y.; Hartley, B. J.; Mukherjee, S.; Tomishima, M.; Brennand, K. J.; Zhang, Q.; Schwartz, R. E.; Evans, T.; Studer, L.; Chen, S.
Article Title:	High-content screening in hPSC-neural progenitors identifies drug candidates that inhibit Zika virus infection in fetal-like organoids and adult brain
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. © 2017 Elsevier Inc.
Keywords:	human pluripotent stem cells; high content chemical screen; human cortical neuron progenitor cells; human forebrain organoids; zika virus
Journal Title:	Cell Stem Cell
Volume:	21
Issue:	2
ISSN:	1934-5909
Publisher:	Cell Press
Date Published:	2017-08-03
Start Page:	274
End Page:	283.e5
Language:	English
DOI:	10.1016/j.stem.2017.06.017
PROVIDER:	scopus
PMCID:	PMC5553280
PUBMED:	28736217
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85025475900&doi=10.1016%2fj.stem.2017.06.017&partnerID=40&md5=269e8dd5db383bfd9701be521e464758
Notes:	Article -- Export Date: 1 September 2017 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/114827