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

摘要

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 sup ?/? /sup). 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.