T-type calcium channels blockers inhibit HSV-2 infection at the late stage of genome replication
T-type calcium channels blockers inhibit HSV-2 infection at the late stage of genome replication
复制标题
T型钙通道阻滞剂在基因组复制后期抑制HSV-2感染
DOI：
10.1016/j.ejphar.2020.173782
复制
发表时间：
2021-02-05
影响因子：
5
通讯作者：
Liu, Shuwen
中科院分区：
文献类型：
--
作者：
Ding, Liqiong;Jiang, Ping;Liu, Shuwen
单纯疱疹病毒2型（HSV-2）是一种高度传染性的性传播病毒。耐药病毒株的不断出现突出了开发具有不同机制的新型抗HSV-2药物的迫切需要。离子通道控制着广泛的细胞功能，是病毒操纵的有吸引力的靶点。在这里，我们试图通过筛选离子通道调节剂的小文库来鉴定抑制HSV-2感染的新型化合物。结果发现，贝尼地平、乐卡地平、洛美利嗪和米贝拉地尔等T型钙通道阻滞剂对HSV-2感染有抑制作用，而硝苯地平和尼群地平等L型钙通道阻滞剂对HSV-2感染无明显影响。此外，我们发现贝尼地平通过在病毒感染后期抑制病毒基因的表达而发挥抗病毒作用。本研究提示临床上广泛使用的T型钙通道阻滞剂能有效抑制HSV-2感染。这些结果为今后HSV-2感染的机制和药理学研究提供了依据。
Herpes simplex virus type 2 (HSV-2) is a highly contagious sexually transmitted virus. The increasing emergence of drug-resistant viral strains has highlighted the crucial need for the development of new anti-HSV-2 drugs with different mechanisms. Ion channels that govern a wide range of cellular functions represent attractive targets for viral manipulation. Here, we tried to identify novel compounds to suppress HSV-2 infection in vitro by screening a small library with ion channels modulators. We found that several T-type calcium channel blockers including benidipine, lercanidipine, lomerizine and mibefradil inhibited HSV-2 infection, while L-type calcium channel blockers nifedipine and nitrendipine showed no significant effect on HSV-2 infection. Furthermore, we found that benidipine exerted the antiviral effect by suppressing the expression of viral genes in the late stage of viral infection. In conclusion, our study suggested that T-type calcium channel blockers, which are clinically wide used, could effectively inhibit HSV-2 infection. These findings could shed light on the mechanism and pharmacological study for HSV-2 infection in the future.