Identification of Ascomycin against Zika virus infection through screening of natural product library.
Antiviral Res
; 196: 105210, 2021 12.
Article
en En
| MEDLINE
| ID: mdl-34801589
ABSTRACT
Zika virus (ZIKV) infection could lead to Guillain-Barré syndrome in adults and microcephaly in the newborns from infected pregnant women. To date, there is no specific drug for the treatment of ZIKV infection. In this study, we sought to screen inhibitors against ZIKV infection from a natural product library. A ZIKV replicon was used to screen a library containing 1680 natural compounds. We explored the antiviral mechanism of the compound candidate in vitro and in vivo infection models. Ascomycin, a macrolide from Streptomyces hygroscopicus, was identified with inhibitory effect against ZIKV in Vero cells (IC50 = 0.11 µM), hepatoma cell Huh7 (IC50 = 0.38 µM), and glioblastoma cell SNB-19 (IC50 = 0.06 µM), far below the cytotoxic concentrations. Mechanistic study revealed that Ascomycin suppressed ZIKV RNA replication step during the life cycle and the regulation of calcineurin-NFAT pathway maybe involved in this inhibitory effect, independent of innate immunity activation. Moreover, we found that Ascomycin also inhibited the infection of other Flaviviridae members, such as hepatitis C virus and dengue virus. Ascomycin reduced ZIKV load in blood by up to 3500-fold in A129 mice. Meanwhile, the infection in the mice brain was undetectable by immunohistochemistry staining. Together, these findings reveal a critical role of Ascomycin in the inhibition of ZIKV and related viruses, facilitating the development of novel antiviral agents.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antivirales
/
Replicación Viral
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Productos Biológicos
/
Tacrolimus
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Ensayos Analíticos de Alto Rendimiento
/
Virus Zika
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
/
Screening_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Antiviral Res
Año:
2021
Tipo del documento:
Article