<br>通过基于报告病毒的高通量筛选发现日本脑炎病毒感染的新抗病毒药物,Journal of Medical Virology

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通过基于报告病毒的高通量筛选发现日本脑炎病毒感染的新抗病毒药物
Journal of Medical Virology ( IF 6.8 ) Pub Date : 2024-01-18 , DOI: 10.1002/jmv.29382
Chunhong Yin _{1,

2} , Peipei Yang _{1,

3} , Qingcui Xiao ₄ , Peng Sun ₄ , Xuekai Zhang _{1,

3} , Jiaxuan Zhao _{1,

3} , Xue Hu _{1,

2} , Chao Shan _{1,

2,

3,

5}

Affiliation

由乙脑病毒（JEV）引起的日本脑炎（JE）仍然是全球公共卫生问题。目前，尚无批准用于治疗乙脑的特效抗病毒药物。虽然疫苗可用于预防，但它们可能无法覆盖所有高危人群。这强调了对预防和有效的抗乙脑病毒药物的迫切需要。在此背景下，开发了表达纳米荧光素酶（Nluc）的高内涵JEV报告系统，并将其用于商业抗病毒库的高通量筛选（HTS），以识别潜在的JEV候选药物。值得注意的是，这一筛选过程发现了五种具有出色抗病毒活性的药物。进一步的作用机制分析表明，千金藤素是一种临床批准的老药，通过阻断 GTP 与 JEV RNA 依赖性 RNA 聚合酶的结合，直接抑制病毒复制。此外，在小鼠模型中使用千金藤碱治疗可减轻乙脑病毒感染。这些发现值得进一步研究千金藤素作为治疗乙脑病毒感染的新治疗方法的潜在抗乙脑病毒活性。事实证明，这里采用的 HTS 方法是一种准确且方便的方法，有助于抗病毒药物的快速开发。

"点击查看英文标题和摘要"

Novel antiviral discoveries for Japanese encephalitis virus infections through reporter virus-based high-throughput screening

Japanese encephalitis (JE) caused by JE virus (JEV), remains a global public health concern. Currently, there is no specific antiviral drug approved for the treatment of JE. While vaccines are available for prevention, they may not cover all at-risk populations. This underscores the urgent need for prophylaxis and potent anti-JEV drugs. In this context, a high-content JEV reporter system expressing Nanoluciferase (Nluc) was developed and utilized for a high-throughput screening (HTS) of a commercial antiviral library to identify potential JEV drug candidates. Remarkably, this screening process led to the discovery of five drugs with outstanding antiviral activity. Further mechanism of action analysis revealed that cepharanthine, an old clinically approved drug, directly inhibited virus replication by blocking GTP binding to the JEV RNA-dependent RNA polymerase. Additionally, treatment with cepharanthine in mice models alleviated JEV infection. These findings warrant further investigation into the potential anti-JEV activity of cepharanthine as a new therapeutic approach for the treatment of JEV infection. The HTS method employed here proves to be an accurate and convenient approach that facilitates the rapid development of antiviral drugs.

更新日期：2024-01-18

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