Ciclopirox Inhibits Hepatitis B Virus Secretion by Blocking Capsid Assembly

Overview

Journal Nat Commun

Specialty Biology

Date 2019 May 18

PMID 31097716

Citations 30

Authors

Jung-Ah Kang

Songwon Kim

Minji Park

Hyun-Jin Park

Jeong-Hyun Kim

Sanghyeok Park

Jeong-Ryul Hwang

Yong-Chul Kim

Yoon Jun Kim

Yuri Cho

Mi Sun Jin

Sung-Gyoo Park

Affiliations

Soon will be listed here.

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.

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