乙型肝炎发展中的药物

StephenW

Drugs. 2017 Jun 28. doi: 10.1007/s40265-017-0769-2. [Epub ahead of print]
Drugs in Development for Hepatitis B.Dawood A1, Abdul Basit S1, Jayaraj M1, Gish RG2,3,4,5,6.
Author information
1Department of Internal Medicine, Section of Gastroenterology, University of Nevada School of Medicine, Las Vegas, NV, USA.2Department of Internal Medicine, Section of Gastroenterology, University of Nevada School of Medicine, Las Vegas, NV, USA. [email protected].3Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Stanford, CA, USA. [email protected].4Hepatitis B Foundation, Doylestown, PA, USA. [email protected].5Asian Pacific Health Foundation, San Diego, CA, USA. [email protected].6National Viral Hepatitis Roundtable, Washington, DC, USA. [email protected].

AbstractWith high morbidity and mortality worldwide, there is great interest in effective therapies for chronic hepatitis B (CHB) virus. There are currently several dozen investigational agents being developed for treatment of CHB. They can be broadly divided into two categories: (1) direct-acting antivirals (DAAs) that interfere with a specific step in viral replication; and (2) host-targeting agents that inhibit viral replication by modifying host cell function, with the latter group further divided into the subcategories of immune modulators and agents that target other host functions. Included among the DAAs being developed are RNA interference therapies, covalently closed circular DNA (cccDNA) formation and transcription inhibitors, core/capsid inhibitors, reverse transcriptase inhibitors, hepatitis B surface antigen (HBsAg) release inhibitors, antisense oligonucleotides, and helioxanthin analogues. Included among the host-targeting agents are entry inhibitors, cyclophilin inhibitors, and multiple immunomodulatory agents, including Toll-like receptor agonists, immune checkpoint inhibitors, therapeutic vaccines, engineered T cells, and several cytokine agents, including recombinant human interleukin-7 (CYT107) and SB 9200, a novel therapy that is believed to both have direct antiviral properties and to induce endogenous interferon. In this review we discuss agents that are currently in the clinical stage of development for CHB treatment as well as strategies and agents currently at the evaluation and discovery phase and potential future targets. Effective approaches to CHB may require suppression of viral replication combined with one or more host-targeting agents. Some of the recent research advances have led to the hope that with such a combined approach we may have a functional cure for CHB in the not distant future.


PMID:28660478DOI:10.1007/s40265-017-0769-2

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StephenW

药品。 2017年6月28日。doi：10.1007 / s40265-017-0769-2。 [提前印刷]
乙型肝炎发展中的药物
Dawood A1，Abdul Basit S1，Jayaraj M1，Gish RG2,3,4,5,6。
作者信息

1
    内华达大学内科学系，内华达大学医学院胃肠病科，拉斯维加斯，内华达州，美国。
2
    内华达大学内科学系，内华达大学医学院胃肠病科，拉斯维加斯，内华达州，美国。 [email protected]。
3
    美国加州斯坦福大学斯坦福大学医学中心消化内科和肝脏科司。 [email protected]。
4
    乙型肝炎基金会，美国宾夕法尼亚州Doylestown。 [email protected]。
五
    亚太卫生基金会，美国加利福尼亚州圣地亚哥。 [email protected]。
6
    国家病毒性肝炎圆桌会议，美国华盛顿特区。 [email protected]。

抽象

世界各地的发病率和死亡率高，对于慢性乙型肝炎（CHB）病毒的有效治疗有很大的兴趣。目前正在开发用于治疗CHB的十几种研究药物。它们可以大致分为两类：（1）干扰病毒复制中特定步骤的直接作用抗病毒药物（DAAs）;和（2）通过修饰宿主细胞功能来抑制病毒复制的宿主靶向试剂，后一组进一步分为针对其他宿主功能的免疫调节剂和试剂的亚类。正在开发的DAAs中包括RNA干扰治疗，共价闭合的环状DNA（cccDNA）形成和转录抑制剂，核心/衣壳抑制剂，逆转录酶抑制剂，乙型肝炎表面抗原（HBsAg）释放抑制剂，反义寡核苷酸和螺旋黄嘌呤类似物。主要靶向剂包括进入抑制剂，亲环蛋白抑制剂和多种免疫调节剂，包括Toll样受体激动剂，免疫检查点抑制剂，治疗疫苗，工程化T细胞和几种细胞因子试剂，包括重组人白细胞介素-7（CYT107 ）和SB 9200，一种被认为具有直接抗病毒性质和诱导内源性干扰素的新疗法。在本次审查中，我们将讨论目前处于CHB治疗发展的临床阶段的代理商以及目前处于评估和发现阶段以及潜在未来目标的战略和代理。 CHB的有效方法可能需要抑制与一种或多种宿主靶向试剂组合的病毒复制。最近的一些研究进展已经导致希望通过这种组合的方法，我们可以在不久的将来对CHB实施治疗。

结论：
    28660478
DOI：
    10.1007 / s40265-017-0769-2