氯化十六烷基吡啶鎓作为乙型肝炎病毒衣壳装配的新型抑制

StephenW

Biochem Biophys Res Commun. 2018 Jan 15. pii: S0006-291X(18)30103-7. doi: 10.1016/j.bbrc.2018.01.088. [Epub ahead of print]
Cetylpyridinium chloride as a novel inhibitor of hepatitis B viral capsid assembly.Seo HW1, Seo JP1, Kim YJ2, Jung G3.
Author information
1Department of Biological Sciences, College of Natural Sciences, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, 151-747, South Korea.2Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, 110-744, South Korea.3Department of Biological Sciences, College of Natural Sciences, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, 151-747, South Korea. Electronic address: [email protected].

AbstractHepatitis B virus (HBV) infection is a major risk factor for chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC) worldwide. While multiple hepatitis B drugs have been developed, development of drug resistance during treatment or weak efficacies observed in some cases have limited their application. Therefore, there is an urgent need to develop better pharmacological agents for HBV-infected individuals. Here, we identified cetylpyridinium chloride (CPC) as a novel inhibitor of HBV. Using computational analysis of CPC-nucleocapsid proteins, microscale thermophoresis analysis of CPC binding to viral nucleocapsids, and in vitro nucleocapsid formation assays, we found that CPC interacts with dimeric viral nucleocapsid protein (known as core protein or HBcAg). Compared with other HBV inhibitors, such as benzenesulfonamide and sulfanilamide, CPC achieved significantly better reduction of HBV particle number in HepG2.2.15 cell line, a derivative of human HCC cells that stably expresses HBV. Taken together, our results show that CPC inhibits capsid assembly and leads to reduced HBV biogenesis. Thus, CPC is an effective pharmacological agent that can eliminate HBV particles.


KEYWORDS: Antiviral; Capsid assembly inhibitor; Cetylpyridinium chloride; Core protein 149; Hepatitis B virus; Structure-based drug

PMID:29353039DOI:10.1016/j.bbrc.2018.01.088

StephenW

Biochem Biophys Res Commun。 2018年1月15日。pii：S0006-291X（18）30103-7。 doi：10.1016 / j.bbrc.2018.01.088。 [电子版提前打印]
氯化十六烷基吡啶鎓作为乙型肝炎病毒衣壳装配的新型抑制剂。
Seo HW1，Seo JP1，Kim YJ2，Jung G3。
作者信息

1
    首尔国立大学自然科学学院生物科学系，韩国首尔市冠岳区冠岳路599号，151-747。
2
    首尔大学医学院内科与肝脏研究所首尔110-744，韩国。
3
    首尔国立大学自然科学学院生物科学系，韩国首尔市冠岳区冠岳路599号，151-747。电子地址：[email protected]。

抽象

乙型肝炎病毒（HBV）感染是全世界慢性肝病，肝硬化和肝细胞癌（HCC）的主要危险因素。虽然已经开发了多种乙肝药物，但是在治疗过程中发生耐药性或者在某些情况下观察到的微弱功效限制了它们的应用。因此，迫切需要为HBV感染者开发更好的药物。在这里，我们确定氯化十六烷基吡啶（CPC）作为一种新型的HBV抑制剂。使用CPC-核衣壳蛋白的计算机分析，CPC结合病毒核衣壳的微型热泳分析以及体外核衣壳形成实验，我们发现CPC与二聚体病毒核衣壳蛋白（称为核心蛋白或HBcAg）相互作用。与其他HBV抑制剂如苯磺酰胺和磺胺类药物相比，CPC可显着降低稳定表达HBV的人肝癌细胞株HepG2.2.15细胞中HBV颗粒数的减少。综上所述，我们的结果显示CPC抑制衣壳装配并导致HBV生物合成减少。因此，CPC是能够消除HBV颗粒的有效药理剂。
关键词：

抗病毒;衣壳组装抑制剂;氯化十六烷基吡啶核心蛋白149;乙型肝炎病毒;基于结构的药物

结论：
    29353039
DOI：

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