乙型肝炎抗病毒药物发现的现状和未来方向

StephenW

Expert Opin Drug Discov. 2016 Oct 31. [Epub ahead of print]
The current status and future directions of hepatitis B antiviral drug discovery.
Tang L1, Zhao Q2, Wu S2, Cheng J2, Chang J2, Guo JT2.
Author information

    1a Microbiology and Immunology graduate program , Drexel University College of medicine , 3805 Old Easton Road, Doylestown , PA 18902 , USA.
    2b Baruch S. Blumberg Institute , Hepatitis B foundation , 3805 Old Easton Road, Doylestown , PA 18902 , USA.

Abstract
INTRODUCTION:

The current standard care of chronic hepatitis B fails to induce a durable off-drug control of hepatitis B virus (HBV) replication in the majority of treated patients. The primary reasons are its inability to eliminate the covalently closed circular (ccc) DNA, the nuclear form of HBV genome, and restoration of the dysfunctional host antiviral immune response against the virus. Accordingly, discovery and development of therapeutics to completely stop HBV replication, eliminate or functionally inactivate cccDNA as well as activate a functional antiviral immune response against HBV are the primary efforts for finding a cure for chronic hepatitis B. Area covered: Herein, the authors highlight the current efforts of HBV drug discovery and offer their opinions for the future directions of this research. Expert opinion: The authors believe that through a consecutive or overlapping three-stage antiviral and immunotherapy program to: (i) completely stop HBV replication and cccDNA amplification; (ii) reduce viral antigen load and induce HBV surface antigen (HBsAg) seroclearance through eradication or inactivation of cccDNA and RNA interference-mediated degradation of viral mRNA and (iii) activate a functional antiviral immune response against HBV through therapeutic immunization or immunotherapy, a functional cure of chronic HBV infection can be achieved in the majority of chronic HBV carriers.

StephenW

专家药物发现2016年10月31日[
乙型肝炎抗病毒药物发现的现状和未来方向。
Tang L1，Zhao Q2，Wu S2，Cheng J2，Chang J2，Guo JT2。
作者信息

    1a微生物学和免疫学研究生课程，Drexel大学医学院，3805 Old Easton Road，Doylestown，PA 18902，USA。
    2b Baruch S.Blumberg Institute，Hepatitis B foundation，3805 Old Easton Road，Doylestown，PA 18902，USA。

抽象
介绍：

目前对慢性乙型肝炎的标准治疗在大多数治疗的患者中不能诱导对乙型肝炎病毒（HBV）复制的持久的非药物控制。主要原因是其不能消除共价闭合的环状（ccc）DNA，HBV基因组的核形式，以及针对病毒的功能失调的宿主抗病毒免疫应答的恢复。因此，发现和开发治疗剂以完全阻止HBV复制，消除或功能性灭活cccDNA以及激活针对HBV的功能性抗病毒免疫应答是寻找治疗慢性乙型肝炎的主要努力。所涵盖的领域：目前乙型肝炎病毒药物发现的努力，并为本研究的未来方向提出他们的意见。专家意见：作者认为，通过连续或重叠的三阶段抗病毒和免疫治疗程序：​​（i）完全停止HBV复制和cccDNA扩增; （ii）通过根除或灭活cccDNA和RNA干扰介导的病毒mRNA降解来减少病毒抗原负载和诱导HBV表面抗原（HBsAg）血清清除，和（iii）通过治疗性免疫或免疫治疗激活针对HBV的功能性抗病毒免疫应答，慢性HBV感染的功能性治愈可以在大多数慢性HBV携带者中实现。

newchinabok

理想太丰满，现实太骨感

StephenW

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专家意见：作者认为，通过连续或重叠的三阶段抗病毒和免疫治疗程序 - 这是基本的目的, 可实现.