Journal
CELL STEM CELL
Volume 21, Issue 2, Pages 274-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2017.06.017
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Funding
- NIH [DP2 DK098093-01, DP3DK111907-01, R01MH101454, R01MH106056, 1R21AI117213, 1K08DK101754]
- Family Friendly Postdoctoral (FFPI) program at Weill Cornell
- F30 predoctoral fellowship from the National Institute of Mental Health [F30 MH113343-01A1]
- training grant from the National Institute of General Medical Sciences [T32GM007739]
- Brain and Behavior Research Foundation
- Brain Research Foundation
- New York Stem Cell Foundation
- NYSTEM Shared Facility contract [C029156, C029153]
- Core support grant from NCI/NIH [P30CA008748]
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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.
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