Glycosylated diphyllin as a broad-spectrum antiviral agent against Zika virus.
EBioMedicine
; 47: 269-283, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-31501074
ABSTRACT
BACKGROUND:
Flaviviruses such as Zika cause sporadic pandemic outbreaks worldwide. There is an urgent need for anti-Zika virus (ZIKV) drugs to prevent mother-to-child transmission of ZIKV, new infections in high-risk populations, and the infection of medical personnel in ZIKV-affected areas.METHODS:
Here, we showed that the small molecule 6-deoxyglucose-diphyllin (DGP) exhibited anti-ZIKV activity both in vitro and in vivo. DGP potently blocked ZIKV infection across all human and monkey cell lines tested. DGP also displayed broad-spectrum antiviral activity against other flaviviruses. Remarkably, DGP prevented ZIKV-induced mortality in mice lacking the type I interferon receptor (Ifnar1-/-). Cellular and virological experiments showed that DGP blocked ZIKV at a pre-fusion step or during fusion, which prevented the delivery of viral contents into the cytosol of the target cell. Mechanistic studies revealed that DGP prevented the acidification of endosomal/lysosomal compartments in target cells, thus inhibiting ZIKV fusion with cellular membranes and infection.FINDINGS:
These investigations revealed that DGP inhibits ZIKV infection in vitro and in vivo.INTERPRETATION:
The small molecule DGP has great potential for preclinical studies and the ability to inhibit ZIKV infection in humans.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Lignanas
/
Benzodioxóis
/
Zika virus
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article