Sun Weikang, Luo Renjie, Qu Qingwei, Yang Jie, Yang Guang, Song Lihua, Cao Peng, Li Erguang
State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing 210093, China.
Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China.
J Agric Food Chem. 2025 Jul 9;73(27):17014-17023. doi: 10.1021/acs.jafc.5c04281. Epub 2025 Jun 25.
Plant-based phenolic components and their metabolites, such as ellagic acid (EA) and urolithin A (UA), possess a variety of biological activities. Here, we investigated the antiviral effect of EA and UA against HSV-1 infection, a virus that causes peripheral infection as well as brain inflammation. Both compounds demonstrated potent antiviral activity. Network pharmacology and molecular docking analyses identified protein kinase CK2 as a common target for their action. We showed that both EA and UA were direct CK2 inhibitors using an enzymatic assay, an observation substantiated in cell culture studies. The effect of EA and UA on HSV-1 infection through CK2 was confirmed in CK2 (CSNK2B) knockout cells. Finally, we demonstrated an antiviral effect using a murine model of herpetic stromal keratitis. EA or UA treatment reduced HSV-1 shedding and prevented viral neuroinvasion. CK2 is a critical enzyme involved in cell proliferation and the proinflammatory response. In addition to identifying CK2 as a putative target of EA and UA antiviral activities, this study also demonstrates that EA and its metabolite UA have the potential to reduce infection-associated neurodegenerative inflammation.
植物源酚类成分及其代谢产物，如鞣花酸（EA）和尿石素A（UA），具有多种生物活性。在此，我们研究了EA和UA对单纯疱疹病毒1型（HSV-1）感染的抗病毒作用，该病毒可引起外周感染以及脑部炎症。这两种化合物均表现出强大的抗病毒活性。网络药理学和分子对接分析确定蛋白激酶CK2是它们作用的共同靶点。我们通过酶活性测定表明，EA和UA都是直接的CK2抑制剂，这一观察结果在细胞培养研究中得到了证实。在CK2（CSNK2B）基因敲除细胞中证实了EA和UA通过CK2对HSV-1感染的影响。最后，我们使用疱疹性基质性角膜炎小鼠模型证明了其抗病毒作用。EA或UA治疗减少了HSV-1的脱落并防止了病毒神经侵袭。CK2是一种参与细胞增殖和促炎反应的关键酶。除了确定CK2是EA和UA抗病毒活性的假定靶点外，本研究还表明EA及其代谢产物UA有潜力减少感染相关的神经退行性炎症。
