Ciclopirox通过阻断衣壳组装来抑制乙型肝炎病毒的分泌。

StephenW

Nat Commun. 2019 May 16;10(1):2184. doi: 10.1038/s41467-019-10200-5.
Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly.
Kang JA1, Kim S1, Park M2, Park HJ1, Kim JH1, Park S1, Hwang JR1, Kim YC1, Jun Kim Y3, Cho Y4, Sun Jin M5, Park SG6.
Author information

1
    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
2
    Department of Internal Medicine, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, 06125, Republic of Korea.
3
    Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
4
    Department of Internal Medicine, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, 06125, Republic of Korea. [email protected].
5
    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea. [email protected].
6
    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea. [email protected].

Abstract

Chronic hepatitis B virus (HBV) infection can cause cirrhosis and hepatocellular carcinoma and is therefore a serious public health problem. Infected patients are currently treated with nucleoside/nucleotide analogs and interferon α, but this approach is not curative. Here, we screen 978 FDA-approved compounds for their ability to inhibit HBV replication in HBV-expressing HepG2.2.15 cells. We find that ciclopirox, a synthetic antifungal agent, strongly inhibits HBV replication in cells and in mice by blocking HBV capsid assembly. The crystal structure of the HBV core protein and ciclopirox complex reveals a unique binding mode at dimer-dimer interfaces. Ciclopirox synergizes with nucleoside/nucleotide analogs to prevent HBV replication in cells and in a humanized liver mouse model. Therefore, orally-administered ciclopirox may provide a novel opportunity to combat chronic HBV infection by blocking HBV capsid assembly.

PMID:
    31097716
DOI:
    10.1038/s41467-019-10200-5

StephenW

Nat Commun。 2019年5月16日; 10（1）：2184。 doi：10.1038 / s41467-019-10200-5。
Ciclopirox通过阻断衣壳组装来抑制乙型肝炎病毒的分泌。
Kang JA1，Kim S1，Park M2，Park HJ1，Kim JH1，Park S1，Hwang JR1，Kim YC1，Jun Kim Y3，Cho Y4，Sun Jin M5，Park SG6。
作者信息

1
光州科学技术学院生命科学学院，光州，61005，韩国。
2
CHA大学医学院CHA江南医学中心内科，首尔，06125，韩国。
3
首尔国立大学医学院内科和肝脏研究所，首尔，03080，韩国。
4
CHA大学医学院CHA江南医学中心内科，首尔，06125，韩国。 [email protected]。
五
光州科学技术学院生命科学学院，光州，61005，韩国。 [email protected]。
6
光州科学技术学院生命科学学院，光州，61005，韩国。 [email protected]。

抽象

慢性乙型肝炎病毒（HBV）感染可引起肝硬化和肝细胞癌，因此是严重的公共卫生问题。受感染的患者有时用核苷/核苷酸类似物和干扰素α治疗，但这种方法不能治愈。在这里，我们筛选了978种FDA批准的化合物在HBV表达的HepG2.2.15细胞中抑制HBV复制的能力。我们发现ciclopirox是一种合成的抗真菌剂，通过阻断HBV衣壳组装，强烈抑制细胞和小鼠中的HBV复制。 HBV核心蛋白和环吡酮复合物的晶体结构揭示了二聚体 - 二聚体界面的独特结合模式。 Ciclopirox与核苷/核苷酸类似物协同作用以预防细胞和人源化肝脏小鼠模型中的HBV复制。口服给予环吡酮可通过阻断HBV衣壳组装来提供抗击慢性HBV感染的新机会。

结论：
31097716
DOI：
10.1038 / s41467-019-10200-5

StephenW

https://www.nature.com/articles/s41467-019-10200-5.pdf