Antiviral activity of PHA767491 against human herpes simplex virus in vitro and in vivo.
Antiviral activity of PHA767491 against human herpes simplex virus in vitro and in vivo.
复制标题
PHA767491对人单纯疱疹病毒的体外和体内抗病毒活性
DOI：
10.1186/s12879-017-2305-0
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发表时间：
2017-03-20
影响因子：
3.7
通讯作者：
He S
中科院分区：
文献类型：
--
作者：
Hou J;Zhang Z;Huang Q;Yan J;Zhang X;Yu X;Tan G;Zheng C;Xu F;He S
BackgroundHerpes simplex virus (HSV) is a common human pathogen that causes a variety of diseases, including oral-labial, genital lesions and life-threatening encephalitis. The antiviral nucleoside analogues such as acyclovir are currently used in anti-HSV therapies; however, clinical overuse of these drugs has led to the emergence of drug-resistant viral strains. Hence, there is an urgent need to develop new anti-HSV agents.MethodsTo identify novel anti-HSV-1 compounds, we screened the LOPAC small scale library of 1280 bioactive compounds to identify inhibitors of HSV-1-induced necroptosis. Further experiments including western blot analysis, Q-PCR analysis and immunohistochemistry were performed to explore the antiviral mechanism of the compounds.ResultsHere, we identified PHA767491 as a new inhibitor of HSV. PHA767491 potently blocked the proliferation of HSV in cells, as well as HSV induced cell death. Further, we found that PHA767491 strongly inhibited HSV infection post viral entry. Moreover, PHA767491 reduced the expression of viral genes required for DNA synthesis including UL30/42 DNA polymerase and UL5/8/52 helicase-primase complex. The essential immediate early (IE) genes such asICP4andICP27are critical for the expression of the early and late genes. Of note, PHA767491 inhibited the expression of all IE genes of both HSV-1 and HSV-2. Importantly, PHA767491 reduced viral titers in the tissues from the mice infected with HSV-1. Consistently, immunohistochemistry analysis showed that PHA767491 dramatically attenuated expression of viral protein gB in the livers.ConclusionsTaken together, PHA767491 has potent anti-HSV activity by inhibiting viral replication both in vitro and in mouse model. Thus, PHA767491 could be a promising agent for the development of new anti-HSV therapy.
