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EBioMedicine 2019 Sep;47:269-83

Glycosylated diphyllin as a broad-spectrum antiviral agent against Zika virus.

Martinez-Lopez A, Persaud M, Chavez MP, Zhang H, Rong L, Liu S, Wang TT, Sarafianos SG, Diaz-Griffero F


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.

Category: Journal Article
PubMed ID: #31501074 DOI: 10.1016/j.ebiom.2019.08.060
PubMed Central ID: #PMC6796538
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2019-09-15 Entry Last Modified: 2020-02-09