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

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.

SUBMITTER: Martinez-Lopez A

PROVIDER: S-EPMC6796538 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Martinez-Lopez Alicia A Persaud Mirjana M Chavez Maritza Puray MP Zhang Hongjie H Rong Lijun L Liu Shufeng S Wang Tony T TT Sarafianos Stefan G SG Diaz-Griffero Felipe F

EBioMedicine 20190906

<h4>Background</h4>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.<h4>Methods</h4>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 m ...[more]

PMID: 31501074

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

Publications

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

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