Department of Microbiology and Immunology, Des Moines University, Des Moines, IA, United States.
Department of Microbiology and Immunology, Des Moines University, Des Moines, IA, United States.
Virus Res. 2018 Apr 2;249:93-98. doi: 10.1016/j.virusres.2018.03.015. Epub 2018 Mar 28.
Herpes Simplex Virus (HSV) is the cause of cold sores, blindness and encephalitis and often leads to recurrent infections. Use of current anti-viral therapies can be limited when drug resistant HSV mutants arise. Thus, novel drugs for the treatment of HSV are needed. Previous research in our laboratory has determined that the telomerase inhibitor, MST-312, interferes with multiple steps of the HSV life cycle. The structure of MST-312 contains moieties related to a natural compound found in green tea, epigallocatechin gallate (EGCG). EGCG has been reported to possess direct virucidal activities toward HSV-1. Here, we tested the virucidal activity of MST-312 and compared it to that of EGCG. Specifically, HSV-1 was exposed to various concentrations of MST-312 or EGCG for time periods between 1 and 60 min and then the ability of the treated virions to form plaques on Vero cells was assessed. When treated for 60 min, 40 μM MST-312 and 0.5-1.0 μM EGCG significantly reduced the number of HSV-1 plaque forming units. The temperature at which treatment occurred impacted the ability of the compounds to limit viral replication. Both compounds were effective when treatment occurred at 37 °C and room temperature (RT). However, no inhibition was seen when virions were treated with MST-312 at 4 °C. 1 min treatment with 2 μM EGCG at RT was sufficient to significantly reduce HSV titers. Higher concentrations of MST-312 were required to inactivate HSV-1 virions compared to EGCG. These data indicate that both EGCG and MST-312 possess direct virucidal properties on HSV-1.
单纯疱疹病毒（HSV）是导致唇疱疹、失明和脑炎的原因，并且经常导致复发性感染。当出现耐药性 HSV 突变体时，目前的抗病毒疗法的使用可能会受到限制。因此，需要新型的 HSV 治疗药物。我们实验室之前的研究已经确定，端粒酶抑制剂 MST-312 干扰 HSV 生命周期的多个步骤。MST-312 的结构包含与绿茶中发现的天然化合物表没食子儿茶素没食子酸酯（EGCG）相关的部分。已经报道 EGCG 对 HSV-1 具有直接的病毒杀伤活性。在这里，我们测试了 MST-312 的病毒杀伤活性，并将其与 EGCG 进行了比较。具体来说，将 HSV-1 暴露于不同浓度的 MST-312 或 EGCG 中 1 至 60 分钟，然后评估处理后的病毒粒子在 Vero 细胞上形成噬菌斑的能力。当处理 60 分钟时，40μM MST-312 和 0.5-1.0μM EGCG 显著减少了 HSV-1 噬菌斑形成单位的数量。处理发生的温度会影响化合物限制病毒复制的能力。当处理发生在 37°C 和室温（RT）时，这两种化合物都有效。然而，当病毒在 4°C 下用 MST-312 处理时，没有观察到抑制作用。在 RT 下用 2μM EGCG 处理 1 分钟足以显著降低 HSV 滴度。与 EGCG 相比，需要更高浓度的 MST-312 才能使 HSV-1 病毒失活。这些数据表明，EGCG 和 MST-312 对 HSV-1 均具有直接的病毒杀伤特性。
