Posaconazole inhibits dengue virus replication by targeting oxysterol-binding protein
Posaconazole inhibits dengue virus replication by targeting oxysterol-binding protein
复制标题
泊沙康唑通过靶向氧甾醇结合蛋白抑制登革热病毒复制
DOI：
10.1016/j.antiviral.2018.06.017
复制
发表时间：
2018-09-01
影响因子：
7.6
通讯作者：
van Rij, Ronald P.
中科院分区：
文献类型：
--
作者：
Meutiawati, Febrina;Bezemer, Bodine;van Rij, Ronald P.
Dengue virus (DENV) is associated with an estimated 390 million infections per year, occurring across approximately 100 countries in tropical and sub-tropical regions. To date, there are no antiviral drugs or specific therapies to treat DENV infection. Posaconazole and itraconazole are potent antifungal drugs that inhibit ergosterol biosynthesis in fungal cells, but also target a number of human proteins. Here, we show that itraconazole and posaconazole have antiviral activity against DENV. Posaconazole inhibited replication of multiple serotypes of DENV and the related flavivirus Zika virus, and reduced viral RNA replication, but not translation of the viral genome. We used a combination of knockdown and drug sensitization assays to define the molecular target of posaconazole that mediates its antiviral activity. We found that knockdown of oxysterol-binding protein (OSBP) inhibited DENV replication. Moreover, knockdown of OSBP, but not other known targets of posaconazole, enhanced the inhibitory effect of posaconazole. Our findings imply OSBP as a potential target for the development of antiviral compounds against DENV.
