Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314, USA.
Antimicrob Agents Chemother. 2011 Dec;55(12):5646-53. doi: 10.1128/AAC.05531-11. Epub 2011 Sep 26.
Topical microbicides are potentially an alternative method to vaccines for reducing the spread of herpes simplex virus (HSV). We have previously shown (S. Liu et al., Biochim. Biophys. Acta 1723:270-281, 2005) that the catechin (-)-epigallocatechin gallate (EGCG) inactivates HSV at neutral pH; however, to function in the female genital tract EGCG must also be effective at acidic pH. EGCG inactivated HSV-1 and HSV-2 at pH 8.0 by 3 log(10) to 4 log(10) but was ineffective at pH 5.7. The EGCG digallate dimers theasinensin A, P2, and theaflavin-3,3'-digallate (TF-3) inactivated both viruses by 3 log(10) to 4 log(10) at pH 5.7 and as much as 5 log(10) at pH 8.0. TF-3 inactivated HSV-1 and HSV-2 by 4 to 5 log(10) in the pH range of 4.0 to 5.7. Dimers with one gallate moiety had antiviral activity intermediate between the activities of EGCG and digallate dimers. Confocal and electron microscopy showed that theasinensin A did not damage Vero cells. All EGCG dimers inactivated enveloped viruses with class I, class II, and class III (HSV-1, HSV-2) fusion proteins more effectively than did monomeric EGCG. EGCG had no activity against the nonenveloped viruses tested, but TF-3 reduced the titer of 4 of 5 nonenveloped viruses by ≅2 to 3.5 log(10). Results also showed that HSV-1 glycoprotein B (gB) was aggregated more rapidly by theasinensin A than EGCG, which, when taken together with the nonenveloped virus data, suggests that dimers may inhibit the function of viral proteins required for infectivity. Digallate dimers of EGCG appear to have excellent potential as microbicidal agents against HSV at acidic and neutral pHs.
局部杀菌剂可能是一种替代疫苗的方法，用于减少单纯疱疹病毒（HSV）的传播。我们之前已经表明（S. Liu 等人，生物化学。生物物理。学报 1723:270-281, 2005），在中性 pH 值下，儿茶素（-）-表没食子儿茶素没食子酸酯（EGCG）使 HSV 失活；然而，为了在女性生殖道中发挥作用，EGCG 也必须在酸性 pH 值下有效。EGCG 在 pH 值为 8.0 时使 HSV-1 和 HSV-2 失活 3 到 4 个对数，但在 pH 值为 5.7 时无效。EGCG 二没食子酸酯二聚体 theasinensin A、P2 和茶黄素-3,3'-二没食子酸酯（TF-3）在 pH 值为 5.7 时使两种病毒失活 3 到 4 个对数，在 pH 值为 8.0 时失活高达 5 个对数。TF-3 在 pH 值为 4.0 到 5.7 的范围内使 HSV-1 和 HSV-2 失活 4 到 5 个对数。具有一个没食子酸酯部分的二聚体具有介于 EGCG 和二聚体之间的抗病毒活性。共聚焦和电子显微镜显示，theasinensin A 不会损伤 Vero 细胞。所有 EGCG 二聚体比单体 EGCG 更有效地使具有 I 类、II 类和 III 类（HSV-1、HSV-2）融合蛋白的包膜病毒失活。EGCG 对测试的非包膜病毒没有活性，但 TF-3 使 5 种非包膜病毒中的 4 种病毒滴度降低了约 2 到 3.5 个对数。结果还表明，HSV-1 糖蛋白 B（gB）比 EGCG 更快地被 theasinensin A 聚集，这与非包膜病毒数据一起表明，二聚体可能抑制感染性所需的病毒蛋白的功能。EGCG 的二没食子酸酯似乎具有极好的潜力，可作为酸性和中性 pH 值下针对 HSV 的杀微生物剂。
