Amentoflavone Inhibits HSV-1 and ACV-Resistant Strain Infection by Suppressing Viral Early Infection
Amentoflavone Inhibits HSV-1 and ACV-Resistant Strain Infection by Suppressing Viral Early Infection
复制标题
穗花果黄酮通过抑制病毒早期感染来抑制 HSV-1 和 ACV 耐药菌株感染
DOI：
10.3390/v11050466
复制
发表时间：
2019-05-01
期刊：
影响因子：
4.7
通讯作者：
Wang, Yifei
中科院分区：
文献类型：
--
作者：
Li, Feng;Song, Xiaowei;Wang, Yifei
单纯疱疹病毒1型（HSV-1）感染可引起严重的临床病症，如单纯疱疹病毒性脑炎和角膜炎。无环鸟苷（Acyclovir，ACV）是目前治疗病毒感染的主要药物，但随着ACV耐药株的逐渐出现，对新型抗病毒药物的需求日益增加。在这项研究中，我们展示了穗花杉双黄酮，一种天然存在的双黄酮，对HSV-1和ACV耐药株的抗病毒活性。穗花杉双黄酮在高浓度下对HSV-1（F株）及HSV-1/106、HSV-1/153、HSV-1/Blue等ACV耐药株均有明显的抑制作用。加药时间试验进一步表明穗花杉双黄酮主要抑制HSV-1早期感染。更详细的研究表明，穗花杉双黄酮影响cofilin介导的F-actin重组，并减少HSV-1从细胞膜到细胞核的细胞内运输。此外，穗花杉双黄酮大大降低了病毒立即早期基因的转录。综上所述，穗花杉双黄酮对HSV-1和ACV耐药株具有较强的抗病毒活性，有望成为HSV-1致病机制的潜在治疗药物。
Infection of Herpes simplex virus 1 (HSV-1) induces severe clinical disorders, such as herpes simplex encephalitis and keratitis. Acyclovir (ACV) is the current therapeutic drug against viral infection and ACV-resistant strains have gradually emerged, leading to the requirement for novel antiviral agents. In this study, we exhibited the antiviral activity of amentoflavone, a naturally occurring biflavonoid, toward HSV-1 and ACV-resistant strains. Amentoflavone significantly inhibited infection of HSV-1 (F strain), as well as several ACV-resistant strains including HSV-1/106, HSV-1/153 and HSV-1/Blue at high concentrations. Time-of-drug-addition assay further revealed that amentoflavone mainly impaired HSV-1 early infection. More detailed study demonstrated that amentoflavone affected cofilin-mediated F-actin reorganization and reduced the intracellular transportation of HSV-1 from the cell membrane to the nucleus. In addition, amentoflavone substantially decreased transcription of viral immediate early genes. Collectively, amentoflavone showed strong antiviral activity against HSV-1 and ACV-resistant strains, and amentoflavone could be a promising therapeutic candidate for HSV-1 pathogenesis.