As a previously neglected member of flavivirus,Zika virus(ZIKV)has recently emerged and caused a global health concern because of its link to microcephaly and other congenital defects.Currently,no anti-ZIKV vaccine or...As a previously neglected member of flavivirus,Zika virus(ZIKV)has recently emerged and caused a global health concern because of its link to microcephaly and other congenital defects.Currently,no anti-ZIKV vaccine or therapy is commercially available.In this drug-screening study,tolvaptan,an FDA-approved drug,was identified to possess the activity against ZIKV strains of Asian lineage with low cytotoxicity using plaque and MTT assays.The anti-ZIKV activity of tolvaptan was also demonstrated using virus yield reduction assay and Western blotting analysis.Time-of-drug-addition assay showed that tolvaptan exerted its anti-ZIKV activity between 6 and 14 h post-ZIKV inoculation,concurrent with the post-entry events of ZIKV life cycle.Tolvaptan also exhibited inhibitory effects on ZIKV strains of African lineage,indicating that its anti-ZIKV activity was not strain dependent.Notably,tolvaptan could also reduce ZIKV-induced mortality in infected mice.Overall,these results suggested that tolvaptan was a potential therapeutic candidate against ZIKV that is worth further evaluation.展开更多
基金National Key R&D Program of China(Grant No.2016YFC1201000)the Key Deployment Projects of the Chinese Academy of Sciences(Grant No.ZDRW-ZS-2016-4-2)the Key Laboratory of Bioactive Peptides of Yunnan Province(Grant No.AMHD-2017-3).
文摘As a previously neglected member of flavivirus,Zika virus(ZIKV)has recently emerged and caused a global health concern because of its link to microcephaly and other congenital defects.Currently,no anti-ZIKV vaccine or therapy is commercially available.In this drug-screening study,tolvaptan,an FDA-approved drug,was identified to possess the activity against ZIKV strains of Asian lineage with low cytotoxicity using plaque and MTT assays.The anti-ZIKV activity of tolvaptan was also demonstrated using virus yield reduction assay and Western blotting analysis.Time-of-drug-addition assay showed that tolvaptan exerted its anti-ZIKV activity between 6 and 14 h post-ZIKV inoculation,concurrent with the post-entry events of ZIKV life cycle.Tolvaptan also exhibited inhibitory effects on ZIKV strains of African lineage,indicating that its anti-ZIKV activity was not strain dependent.Notably,tolvaptan could also reduce ZIKV-induced mortality in infected mice.Overall,these results suggested that tolvaptan was a potential therapeutic candidate against ZIKV that is worth further evaluation.
