Wedelolactone (WDL) is a coumestan present in the plants Eclipta prostrata and Wedelia calendulacea which are used for treatment of a multitude of health problems in traditional medicine. It has previously been shown that WDL exerts antiviral activity against human immunodeficiency virus and hepatitis C virus. In this study, we investigated the effect of WDL on lytic human cytomegalovirus (HCMV) infection. We demonstrate a strong interference with HCMV replication as analyzed in multi-round replication settings. A more detailed analysis of the underlying mechanisms revealed that WDL acts at two distinct steps of the viral replication cycle. During immediate early (IE) times, we observe an inhibition of IE1/IE2 expression. Although WDL was reported to interfere with NF-κB signaling our results suggest the existence of additional mechanisms that impede viral IE expression. During later time points of infection, WDL induced a disruption of the interaction between EZH2 and EED, components of the virus-supportive polycomb repressive complex 2 (PRC2). Thereby, the stability of the PRC2 complex as well as the related complex PRC1 was disturbed leading to diminished viral DNA synthesis. Taken together, we identify WDL as a potent agent against HCMV which interferes at two distinct steps of viral replication.

中文翻译：

---

Wedelolactone通过靶向病毒复制周期的不同步骤来抑制人类巨细胞病毒复制。

Wedelolactone（WDL）是存在于Eclipta prostrata和Wedelia calendulacea植物中的一种香豆素，可用于治疗传统医学中的许多健康问题。先前已证明WDL对人免疫缺陷病毒和丙型肝炎病毒发挥抗病毒活性。在这项研究中，我们调查了WDL对溶解性人类巨细胞病毒（HCMV）感染的影响。如在多轮复制设置中分析的，我们证明了对HCMV复制的强烈干扰。对基本机制的更详细分析显示，WDL在病毒复制周期的两个不同步骤中起作用。在立即早期（IE）时间，我们观察到IE1 / IE2表达的抑制。尽管据报道WDL会干扰NF-κB信号传导，但我们的研究结果表明存在阻止病毒IE表达的其他机制。在以后的感染时间点，WDL诱导了EZH2和EED之间的相互作用中断，EZH2和EED是病毒支持的多梳抑制复合物2（PRC2）的组成部分。因此，PRC2复合物以及相关复合物PRC1的稳定性被破坏，导致病毒DNA合成减少。两者合计，我们确定WDL是抗HCMV的有效剂，它会干扰病毒复制的两个不同步骤。PRC2复合物以及相关复合物PRC1的稳定性受到干扰，导致病毒DNA合成减少。两者合计，我们确定WDL是抗HCMV的有效剂，它会干扰病毒复制的两个不同步骤。PRC2复合物以及相关复合物PRC1的稳定性受到干扰，导致病毒DNA合成减少。两者合计，我们确定WDL是抗HCMV的有效剂，它会干扰病毒复制的两个不同步骤。