Stamos James D, Lee Lee H, Taylor Calvin, Elias Tony, Adams Sandra D
Biology Department, Montclair State University, Montclair, NJ 07043, USA.
Microorganisms. 2022 Jul 20;10(7):1462. doi: 10.3390/microorganisms10071462.
About half a billion people worldwide are infected with herpes simplex virus-2 (HSV-2). Prolonged treatment with acyclovir (ACV) and its analogs leads to the development of resistant strains. The aim of this study was to investigate the antiviral potential of epigallocatechin gallate (EGCG) from and a stable analog EGCG-stearate (EGCG-S) against HSV-2 in cultured Vero cells. Cell viability and cell proliferation assays were used to determine the non-cytotoxic concentrations on cultured Vero cells. HSV-2 with a green fluorescent protein (GFP) fusion protein of VP26 virions were treated with non-cytotoxic concentrations of EGCG and EGCG-S. The effects on infectivity and mechanisms were determined by plaque assay, attachment and penetration assays, confocal microscopy, qPCR, and in silico modeling analysis. Our results demonstrate that treatment of HSV-2 virions with EGCG and EGCG-S at a concentration of 75 µM showed greater than 99.9% inhibition by inhibiting the attachment of HSV-2 virions to host cells. The bioinformatic analysis indicated high binding affinity of EGCG-S for glycoprotein D; thus EGCG-S may block fusion of HSV-2 and the cell membrane, preventing entry of HSV-2 into the cell.
全球约有5亿人感染单纯疱疹病毒2型（HSV-2）。长期使用阿昔洛韦（ACV）及其类似物进行治疗会导致耐药菌株的产生。本研究的目的是研究表没食子儿茶素没食子酸酯（EGCG）及其稳定类似物表没食子儿茶素硬脂酸酯（EGCG-S）在培养的非洲绿猴肾细胞（Vero细胞）中对HSV-2的抗病毒潜力。采用细胞活力和细胞增殖试验来确定对培养的Vero细胞无细胞毒性的浓度。用无细胞毒性浓度的EGCG和EGCG-S处理带有病毒蛋白26（VP26）绿色荧光蛋白融合蛋白的HSV-2。通过空斑试验、吸附和穿透试验、共聚焦显微镜、定量聚合酶链反应（qPCR）和计算机模拟分析来确定其对感染性和作用机制的影响。我们的结果表明，用浓度为75µM的EGCG和EGCG-S处理HSV-2病毒体，通过抑制HSV-2病毒体与宿主细胞的吸附，显示出大于99.9%的抑制率。生物信息学分析表明EGCG-S与糖蛋白D具有高结合亲和力；因此，EGCG-S可能会阻断HSV-2与细胞膜的融合，防止HSV-2进入细胞。
