Antiviral activity of the adenosine analogue BCX4430 against West Nile virus and tick-borne flaviviruses
Antiviral activity of the adenosine analogue BCX4430 against West Nile virus and tick-borne flaviviruses
复制标题
DOI：
10.1016/j.antiviral.2017.03.012
复制
发表时间：
2017-06-01
影响因子：
7.6
通讯作者：
Ruzek, Daniel
中科院分区：
文献类型：
--
作者：
Eyer, Ludek;Zouharova, Darina;Ruzek, Daniel
目前尚无针对医学上重要的人类黄病毒的获批抗病毒疗法。亚氨基-C-核苷BCX 4430对多种RNA病毒显示出广谱抗病毒活性。在这里，我们证明了BCX 4430抑制黄病毒属的蜱传物种;然而，抗病毒效果因物种而异。微摩尔BCX 4430水平抑制蜱传脑炎病毒（TBEV）;而抑制Louping病病毒和Kyasanur森林病病毒需要约3-8倍的浓度。此外，该化合物强烈抑制西尼罗河病毒（一种典型的蚊子传播的黄病毒）的体外复制。比较了该化合物的两种化学形式，即BCX 4430和BCX 4430盐酸盐，两者在我们的体外抗病毒测定系统中表现出相似的抑制特性，在猪肾稳定细胞和Vero细胞中没有或可忽略不计的细胞毒性。所获得的数据表明，除了蚊媒黄病毒外，该化合物对TBEV血清复合物的成员具有强的抗病毒活性。(C)2017爱思唯尔B. V.保留所有权利。
There are currently no approved antiviral therapies against medically important human flaviviruses. The imino-C-nucleoside BCX4430 shows broad-spectrum antiviral activity against a wide range of RNA viruses. Here, we demonstrate that BCX4430 inhibits tick-borne species of the genus Flavivirus; however, the antiviral effect varies against individual species. Micro-molar BCX4430 levels inhibited tick-borne encephalitis virus (TBEV); while, approximately 3-8-fold higher concentrations were needed to inhibit louping ill virus and Kyasanur Forest disease virus. Moreover, the compound strongly inhibited in vitro replication of West Nile virus, a typical mosquito-transmitted flavivirus. Two chemical forms of the compound, i.e. BCX4430 and BCX4430 hydrochloride, were compared and both exerted similar inhibitory profiles in our in vitro antiviral assay systems and no or negligible cytotoxicity in porcine kidney stable and Vero cells. The obtained data indicate that, in addition to mosquito-borne flaviviruses, the compound has strong antiviral activity against members of the TBEV serocomplex. (C) 2017 Elsevier B.V. All rights reserved.