RNA依赖性RNA聚合酶作为抗戊型肝炎病毒药物作用靶点的研究进展

doi:10.16431/j.cnki.1671-7236.2024.10.037

中国畜牧兽医 ›› 2024, Vol. 51 ›› Issue (10): 4568-4577.doi: 10.16431/j.cnki.1671-7236.2024.10.037

• 基础兽医 • 上一篇

RNA依赖性RNA聚合酶作为抗戊型肝炎病毒药物作用靶点的研究进展

何振文^1,2,4, 刘丁语^1,3, 刘宝玲¹, 张翩¹, 王晓虎¹, 王刚¹, 黄元¹, 陈晶¹, 刘文俊², 蔡汝健¹

1. 广东省农业科学院动物卫生研究所, 广东省畜禽疫病防治研究重点实验室, 农业农村部兽用药物与诊断技术广东科学观测实验站, 广州 510640;
2. 仲恺农业工程学院动物科技学院, 广州 510225;
3. 华中农业大学动物医学院, 生猪健康养殖协同创新中心, 武汉 430000;
4. 东莞市中堂镇农业技术服务中心, 东莞 523220

收稿日期:2024-03-20 发布日期:2024-09-30
通讯作者: 蔡汝健 E-mail:466866569@qq.com
作者简介:何振文，E-mail:331424732@qq.com。
基金资助:
广东省省级科技计划项目(2023B0202010014)；2021年英德市科技计划项目；云浮市云安区生猪产业园科技支撑与技术示范(动卫经合(2022) K06-005号)；生猪智能化动物疫病防疫与诊疗系统(动卫经合(2022) K11-006号)

Research Progress on RdRp as an Action Target for Anti-Hepatitis E Virus Drug

HE Zhenwen^1,2,4, LIU Dingyu^1,3, LIU Baoling¹, ZHANG Pian¹, WANG Xiaohu¹, WANG Gang¹, HUANG Yuan¹, CHEN Jing¹, LIU Wenjun², CAI Rujian¹

1. Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province of Ministry of Agriculture and Rural Affairs, Key Laboratory of Livestock Disease Prevention of Guangdong Province, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510225, China;
2. College of Animal Science & Technology, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China;
3. The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430000, China;
4. Dongguan Zhongtang Town Agricultural Technical Service Center, Dongguan 523220, China

Received:2024-03-20 Published:2024-09-30

摘要/Abstract

摘要： 戊型肝炎病毒(Hepatitis E virus,HEV)是造成急性肝炎最常见的原因之一。HEV基因组由5'非编码区、3个开放阅读框(ORF1、ORF2、ORF3)和3'非编码区组成，仅在HEV-1中发现了ORF4，并与ORF1重叠。各种编码蛋白在HEV的复制和感染中发挥着不同的作用，而HEV的复制是由ORF1编码的RNA依赖性RNA聚合酶(RNA-dependent RNA polymerase,RdRp)所介导的。HEV RdRp是由多个蛋白亚基组成的复合酶，具有7个保守基序，这些保守基序在RNA合成过程中发挥核苷酸识别、合成、延伸、修饰和稳定等作用，保证了RdRp的功能，在HEV的复制和转录中起到关键作用。因此，以RdRp作为抗HEV药物作用靶点的治疗方案具有很好的应用前景，是目前药物开发的一种主流思路。目前，已发现利巴韦林、索非布韦、2'-C-甲基胞苷(2CMC)等核苷类RdRp抑制剂和锌、GPC-N114等非核苷类RdRp抑制剂对HEV有较强的抑制作用，可作为潜在的抗HEV药物进行深入研究。笔者对HEV编码蛋白和HEV RdRp的结构与功能进行阐述，总结目前发现的对HEV有抑制作用的RdRp抑制剂，以期为HEV的药物开发提供一种新的思路。

关键词: 戊型肝炎病毒(HEV); RNA依赖性RNA聚合酶(RdRp); 药物开发

Abstract: Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis.The HEV genome consists of a 5' non-coding region,three open reading frames (ORF1,ORF2 and ORF3),and a 3' non-coding region,with ORF4 found only in HEV-1 and overlapping with ORF1.Various coding proteins play different roles in HEV replication and infection,and HEV replication is mediated by RNA-dependent RNA polymerase (RdRp) encoded by ORF1.HEV RdRp is a complex enzyme composed of multiple protein subunits,with 7 conserved motifs.These conserved motifs play roles in nucleotide recognition,addition,extension,modification,and stabilization during RNA synthesis,ensuring the functionality of RdRp,which plays a crucial role in HEV replication and transcription.Therefore,RdRp as the action target of anti-HEV drug has a good application prospect and is a mainstream idea in drug development.Currently,nucleoside RdRp inhibitors like ribavirin,sofosbuvir and 2CMC,and non-nucleoside RdRp inhibitors like zinc salts,GPC-N114 have shown strong inhibitory effects on HEV and can be potential anti-HEV drugs for further research.The author elaborates on the structure and function of HEV encoding protein and HEV RdRp,and a summary of the RdRp inhibitors that have been discovered to inhibit HEV is provided in order to offer new insights for the development of HEV drugs.

Key words: Hepatitis E virus (HEV); RNA-dependent RNA polymerase (RdRp); drug development

中图分类号:

S852.65
R373

何振文, 刘丁语, 刘宝玲, 张翩, 王晓虎, 王刚, 黄元, 陈晶, 刘文俊, 蔡汝健. RNA依赖性RNA聚合酶作为抗戊型肝炎病毒药物作用靶点的研究进展[J]. 中国畜牧兽医, 2024, 51(10): 4568-4577.

HE Zhenwen, LIU Dingyu, LIU Baoling, ZHANG Pian, WANG Xiaohu, WANG Gang, HUANG Yuan, CHEN Jing, LIU Wenjun, CAI Rujian. Research Progress on RdRp as an Action Target for Anti-Hepatitis E Virus Drug[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(10): 4568-4577.

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RNA依赖性RNA聚合酶作为抗戊型肝炎病毒药物作用靶点的研究进展

Research Progress on RdRp as an Action Target for Anti-Hepatitis E Virus Drug

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