Zika virus (ZIKV) is an arbovirus associated with neurological disorders accompanying congenital infections. With no vaccine or antiviral approved, there is an urgent need for the development of effective antiviral agents against ZIKV infection. We evaluated the anti-ZIKV and immunomodulatory activity of ouabain, a Na+/K+-ATPase inhibitor known to have immunomodulatory and antiviral activities, using human neural stem and progenitor cells (hNS/PCs) and a murine model of congenital Zika syndrome (CZS). Our data demonstrated that ouabain reduces ZIKV infection in hNS/PCs, mouse placenta, yolk sac, and the fetal head. Ouabain mitigated neurogenesis impairment triggered by ZIKV in hNS/PCs and prevented ZIKV-mediated reduction of fetus and head sizes. In addition, ouabain decreased tumor necrosis factor and interleukin-1β levels in the placenta, highlighting its immunomodulatory activity in the murine model. Our findings indicate that ouabain possesses anti-ZIKV and immunomodulatory activities, suggesting that it should be investigated further as a promising treatment for CZS.

中文翻译：

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哇巴因对先天性寨卡综合征模型的抗病毒和免疫调节作用


寨卡病毒 （ZIKV） 是一种虫媒病毒，与伴随先天性感染的神经系统疾病有关。由于没有疫苗或抗病毒药物获得批准，迫切需要开发针对 ZIKV 感染的有效抗病毒药物。我们使用人神经干细胞和祖细胞 （hNS/PCs） 和先天性寨卡综合征 （CZS） 的小鼠模型评估了哇巴因的抗 ZIKV 和免疫调节活性，哇巴因是一种已知具有免疫调节和抗病毒活性的 Na+/K+-ATP 酶抑制剂。我们的数据表明，哇巴因可减少 hNS/PCs、小鼠胎盘、卵黄囊和胎头中的 ZIKV 感染。Ouabain 减轻了 hNS/PCs 中 ZIKV 触发的神经发生障碍，并阻止了 ZIKV 介导的胎儿和头部大小的减小。此外，哇巴因降低了胎盘中的肿瘤坏死因子和白细胞介素-1β 水平，突出了其在小鼠模型中的免疫调节活性。我们的研究结果表明，哇巴因具有抗 ZIKV 和免疫调节活性，表明它应该作为一种有前途的 CZS 治疗方法进行进一步研究。