Synergistic in-vitro antiviral effects of combination treatment using anidulafungin and T-1105 against Zika virus infection
Synergistic in-vitro antiviral effects of combination treatment using anidulafungin and T-1105 against Zika virus infection
复制标题
DOI：
10.1016/j.antiviral.2021.105188
复制
发表时间：
2021-10-21
影响因子：
7.6
通讯作者：
Ho, Yi-Jung
中科院分区：
文献类型：
--
作者：
Lu, Jeng-Wei;Chen, Yen-Chen;Ho, Yi-Jung
自2007年以来，寨卡病毒（ZIKV）一直是一些流行病的原因。小头畸形和格林-巴利综合征与ZIKV的相关性已经被注意到。不幸的是，研究人员尚未开发出有效的疫苗或药物批准用于ZIKV感染。阿尼芬净是棘白菌素的一种，用于治疗念珠菌感染。本研究评估了阿尼芬净对ZIKV的抗病毒能力。阿尼芬净显示出显著降低病毒RNA水平、蛋白质表达水平、病毒产量和感染率。在添加测定时，阿尼芬净在ZIKV感染的早期阶段表现出抑制活性。在结合和进入测定中，施用阿尼芬净不会导致病毒RNA的量的相应减少，但在杀病毒测定中观察到ZIKV感染性的显著降低。这表明阿尼芬净直接干扰病毒体。T-1105是一种病毒聚合酶抑制剂，在ZIKV感染的晚期发挥作用。当阿尼芬净与T-1105联合给药时，观察到明显的协同效应，导致联合指数（CI）值为0.85 +/- 0.13。最后，我们根据半数最大抑制浓度（IC 50）、计算50%细胞毒性浓度（CC 50）、选择性指数（SI）和Patchdock评分评价棘白菌素的作用。在这些测试中，阿尼芬净具有最低的IC 50和最高的Patchdock评分。尽管阿尼芬净被归类为妊娠C类药物;然而，阿尼芬净与病毒RNA复制抑制剂的联合治疗可以扩大ZIKV感染的治疗选择。
Zika virus (ZIKV) has been the cause of some epidemics since 2007. The correlations of microcephaly and Guillain-Barre ' syndrome with ZIKV have been noticed. Unfortunately, researchers have yet to develop an effective vaccine or drug approved for ZIKV infection. Anidulafungin is a member of echinocandins that is used to treat candida infections. This study assessed the antiviral capability of anidulafungin against ZIKV. Anidulafungin was shown to significantly decrease viral RNA levels, protein expression levels, viral yields, and the rate of infection. In time of addition assays, anidulafungin exhibited inhibitory activities in the early stages of ZIKV infection. In binding and entry assays, administering anidulafungin did not lead to a corresponding decrease in quantity of viral RNA, but a significant decrease in ZIKV infectivity was observed in virucidal assays. This indicated that anidulafungin interferes directly with virions. T-1105 is a viral polymerase inhibitor, which functions in the late stage of ZIKV infection. When anidulafungin was administered in combination with T-1105, an obvious synergistic effect was observed, resulting in a combination index (CI) value of 0.85 +/- 0.13. Finally, we evaluated the effects of echinocandins in terms of half-maximal inhibitory concentration (IC50), calculation of cytotoxicity concentration 50% (CC50), selectivity index (SI), and Patchdock score. Among the tests, anidulafungin bears the lowest IC50 and highest Patchdock score. Although anidulafungin is classified as a pregnancy category C agent; however, combination therapy of anidulafungin with a viral RNA replication inhibitor could expand treatment options for ZIKV infection.