High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain.
Cell Stem Cell
; 21(2): 274-283.e5, 2017 08 03.
Article
em En
| MEDLINE
| ID: mdl-28736217
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Encéfalo
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Organoides
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Avaliação Pré-Clínica de Medicamentos
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Células-Tronco Pluripotentes Induzidas
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Células-Tronco Neurais
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Zika virus
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Infecção por Zika virus
Tipo de estudo:
Diagnostic_studies
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Screening_studies
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos