School of Pathology, Faculty of Health Sciences, Wits/SAMRC Antiviral Gene Therapy Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
Expert Opin Ther Targets. 2021 Jun;25(6):451-466. doi: 10.1080/14728222.2021.1915990. Epub 2021 Apr 19.
: Current therapy for infection with hepatitis B virus (HBV) rarely clears the virus, and viremia commonly resurges following treatment withdrawal. To prevent serious complications of the infection, research has been aimed at identifying new viral and host targets that can be exploited to inactivate HBV replication.: This paper reviews the use of these new molecular targets to advance anti-HBV therapy. Emphasis is on appraising data from pre-clinical and early clinical studies described in journal articles published during the past 10 years and available from PubMed.: The wide range of viral and host factors that can be targeted to disable HBV is impressive and improved insight into HBV molecular biology continues to provide the basis for new drug design. In addition to candidate therapies that have direct or indirect actions on HBV covalently closed circular DNA (cccDNA), compounds that inhibit HBsAg secretion, viral entry, destabilize viral RNA and effect enhanced immune responses to HBV show promise. Preclinical and clinical evaluation of drug candidates, as well as investigating use of treatment combinations, are encouraging. The field is poised at an interesting stage and indications are that reliably achieving functional cure from HBV infection is a tangible goal.
: 当前针对乙型肝炎病毒(HBV)感染的治疗方法很少能清除病毒,并且在治疗停药后病毒血症通常会再次出现。为了预防感染的严重并发症,研究旨在确定新的病毒和宿主靶标,以灭活 HBV 复制。: 本文综述了利用这些新的分子靶标来推进抗 HBV 治疗。重点评估了过去 10 年在期刊文章中描述的临床前和早期临床研究的数据,这些数据可从 PubMed 获取。: 可以靶向的广泛的病毒和宿主因子,以灭活 HBV 令人印象深刻,并且对 HBV 分子生物学的深入了解继续为新药设计提供基础。除了对共价闭合环状 DNA(cccDNA)具有直接或间接作用的候选治疗药物外,抑制 HBsAg 分泌、病毒进入、破坏病毒 RNA 以及增强对 HBV 的免疫反应的化合物也显示出前景。药物候选物的临床前和临床评估,以及对治疗联合应用的研究,都令人鼓舞。该领域正处于一个有趣的阶段,有迹象表明,从 HBV 感染中可靠地实现功能性治愈是一个切实可行的目标。