FDA已批准上市药物托伐普坦可在体内外抑制寨卡病毒感染

Tolvaptan,an FDA-approved drug,inhibits Zika virus infection both in vitro and in vivo

寨卡病毒(Zika virus,ZIKV)是黄病毒属中一个被忽视的病毒。近年来,由于其与小头畸形和其他先天性缺陷疾病的关系,引起了全球的广泛关注。目前,仍没有抗ZIKV的疫苗或治疗方法批准上市。我们通过噬斑实验及MTT实验筛选鉴定出一种FDA已批准上市药物--托伐普坦,具有抗亚洲谱系寨卡病毒活性且细胞毒性很低。病毒产量降低实验和蛋白印迹实验也进一步证实了托伐普坦的抗寨卡病毒活性。分时给药实验表明托伐普坦在细胞感染ZIKV后6到14 h发挥抗ZIKV活性,即作用于ZIKV生命周期的进入后阶段。此外,托伐普坦对非洲普系寨卡病毒也具有抑制作用,表明托伐普坦的抗ZIKV活性并不是毒株依赖性的。值得注意的是,托伐普坦还可降低ZIKV感染小鼠的死亡率。因此,托伐普坦是一个潜在的抗ZIKV治疗药物,值得进一步研究。

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.