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