School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China.
Bioorg Med Chem. 2012 Feb 15;20(4):1616-23. doi: 10.1016/j.bmc.2011.11.040. Epub 2011 Nov 30.
Noroviruses (NoVs) are the leading cause of viral acute gastroenteritis affecting people of all ages worldwide. The disease is difficult to control due to its widespread nature and lack of an antiviral or vaccine. NoV infection relies on the interaction of the viruses with histo-blood group antigens (HBGAs) as host receptors. Here we investigated inhibition effects of Chinese medicinal herbs against NoVs binding to HBGAs for potential antivirals against NoVs. Blocking assays was performed using the NoV protrusion (P) protein as NoV surrogate and saliva as HBGAs. Among 50 clinically effective Chinese medicinal herbs against gastroenteritis diseases, two herbs were found highly effective. Chinese Gall blocked NoV P dimer binding to type A saliva at IC(50)=5.35 μg/ml and to B saliva at IC(50)=21.7 μg/ml. Similarly, Pomegranate blocked binding of NoV P dimer to type A saliva at IC(50)=15.59 μg/ml and B saliva at IC(50)=66.67 μg/ml. Literature data on preliminary biochemistry analysis showed that tannic acid is a common composition in the extracts of the two herbs, so we speculate that it might be the effective compound and further studies using commercially available, highly purified tannic acid confirmed the tannic acid as a strong inhibitor in the binding of NoV P protein to both A and B saliva (IC(50)≈0.1 μM). In addition, we tested different forms of hydrolysable tannins with different alkyl esters, including gallic acid, ethyl gallate, lauryl gallate, octyl gallate and propyl gallate. However, none of these tannins-derivatives revealed detectable inhibiting activities. Our data suggested that tannic acid is a promising candidate antiviral against NoVs.
诺如病毒（NoV）是导致全球各年龄段人群病毒性急性肠胃炎的主要原因。由于其广泛传播且缺乏抗病毒药物或疫苗，因此该疾病难以控制。NoV 感染依赖于病毒与组织血型抗原（HBGA）作为宿主受体的相互作用。在这里，我们研究了中草药对 NoV 与 HBGA 结合的抑制作用，以寻找潜在的 NoV 抗病毒药物。使用 NoV 突起（P）蛋白作为 NoV 替代物和唾液作为 HBGA 进行阻断试验。在 50 种针对肠胃炎疾病具有临床疗效的中草药中，有两种草药被发现具有高度的抑制效果。五倍子能阻断 NoV P 二聚体与 A 型唾液的结合，IC50 为 5.35 μg/ml，与 B 型唾液的结合，IC50 为 21.7 μg/ml。同样，石榴能阻断 NoV P 二聚体与 A 型唾液的结合，IC50 为 15.59 μg/ml，与 B 型唾液的结合，IC50 为 66.67 μg/ml。文献中的初步生化分析数据表明，鞣酸是这两种草药提取物中的常见成分，因此我们推测鞣酸可能是有效的化合物，进一步使用市售的、高度纯化的鞣酸进行研究证实了鞣酸是一种强有力的抑制剂，能抑制 NoV P 蛋白与 A 和 B 型唾液的结合（IC50≈0.1 μM）。此外，我们还测试了不同形式的、具有不同烷基酯的水解单宁，包括没食子酸、没食子酸乙酯、没食子酸月桂酯、没食子酸辛酯和没食子酸丙酯。然而，这些单宁衍生物均没有表现出可检测的抑制活性。我们的数据表明，鞣酸是一种有前景的抗 NoV 候选抗病毒药物。
