| Autor: |
Alicia Martinez-Lopez, Mirjana Persaud, Maritza Puray Chavez, Hongjie Zhang, Lijun Rong, Shufeng Liu, Tony T. Wang, Stefan G. Sarafianos, Felipe Diaz-Griffero |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
EBioMedicine, Vol 47, Iss , Pp 269-283 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2019.08.060 |
| Popis: |
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. Keywords: Zika, Glycosylated diphyllin, Fusion, Endosomal, pH, Ifnar1−/− |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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