HBV复制抑制剂。

StephenW

Antiviral Res. 2020 May 4:104815. doi: 10.1016/j.antiviral.2020.104815. [Epub ahead of print]
HBV replication inhibitors.
Rouviere CP1, Dousson CB2, Tavis JE3.
Author information

1
    Ai-biopharma, Medicinal Chemistry Department, Montpellier, France.
2
    Ai-biopharma, Medicinal Chemistry Department, Montpellier, France. Electronic address: [email protected].
3
    Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA. Electronic address: [email protected].

Abstract

Chronic Hepatitis B Virus infections afflict >250 million people and kill nearly 1 million annually. Current non-curative therapies are dominated by nucleos(t)ide analogs (NAs) that profoundly but incompletely suppress DNA synthesis by the viral reverse transcriptase. Residual HBV replication during NA therapy contributes to maintenance of the critical nuclear reservoir of the HBV genome, the covalently-closed circular DNA, and to ongoing infection of naive cells. Identification of next-generation NAs with improved efficacy and safety profiles, often through novel prodrug approaches, is the primary thrust of ongoing efforts to improve HBV replication inhibitors. Inhibitors of the HBV ribonuclease H, the other viral enzymatic activity essential for viral genomic replication, are in preclinical development. The complexity of HBV's reverse transcription pathway offers many other potential targets. HBV's protein-priming of reverse transcription has been briefly explored as a potential target, as have the host chaperones necessary for function of the HBV reverse transcriptase. Improved inhibitors of HBV reverse transcription would reduce HBV's replication-dependent persistence mechanisms and are therefore expected to become a backbone of future curative combination anti-HBV therapies.

Copyright © 2020 Elsevier B.V. All rights reserved.
KEYWORDS:

Chronic hepatitis B; Hepatitis B virus; Nucleos(t)ide analogs; Reverse transcriptase inhibitors; Ribonuclease H inhibitors

PMID:
    32380149
DOI:
    10.1016/j.antiviral.2020.104815

StephenW

抗病毒水库。 2020年5月4：104815。 doi：10.1016 / j.antiviral.2020.104815。 [Epub提前发布]
HBV复制抑制剂。
Rouviere CP1，Dousson CB2，Tavis JE3。
作者信息

1个
    法国蒙彼利埃市药物化学系Ai-biopharma。
2
    法国蒙彼利埃市药物化学系Ai-biopharma。电子地址：[email protected]。
3
    圣路易斯大学医学院分子微生物学和免疫学系，美国密苏里州圣路易斯。电子地址：[email protected]。

抽象

慢性乙型肝炎病毒感染困扰着超过2.5亿人，每年造成近100万人死亡。当前的非治愈性疗法主要由核苷酸（t）核苷酸类似物（NAs）主导，该类似物深刻但不完全抑制病毒逆转录酶合成DNA。在NA治疗期间残留的HBV复制有助于维持HBV基因组的关键核储库，共价闭合的环状DNA以及持续感染幼稚细胞。通常通过新颖的前药方法来鉴定具有改善的疗效和安全性的下一代NA，这是不断努力改善HBV复制抑制剂的主要方向。 HBV核糖核酸酶H的抑制剂是病毒基因组复制所必需的另一种病毒酶活性，目前处于临床前开发阶段。 HBV逆转录途径的复杂性提供了许多其他潜在的靶标。 HBV的逆转录蛋白质引发已被作为潜在的靶标进行了简要探讨，而HBV逆转录酶功能所必需的宿主伴侣也已经被研究。改良的HBV逆转录抑制剂会减少HBV的复制依赖性持久机制，因此有望成为未来抗乙肝病毒治疗联合疗法的骨干。

版权所有©2020 Elsevier B.V.保留所有权利。
关键字：

慢性乙型肝炎；乙型肝炎病毒;核苷类似物;逆转录酶抑制剂；核糖核酸酶H抑制剂

PMID：
    32380149
DOI：
    10.1016 / j.antiviral.2020.104815

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