Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly

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 () and Sung-Gyoo Park ()
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Jung-Ah Kang: Gwangju Institute of Science and Technology
Songwon Kim: Gwangju Institute of Science and Technology
Minji Park: CHA University School of Medicine
Hyun-Jin Park: Gwangju Institute of Science and Technology
Jeong-Hyun Kim: Gwangju Institute of Science and Technology
Sanghyeok Park: Gwangju Institute of Science and Technology
Jeong-Ryul Hwang: Gwangju Institute of Science and Technology
Yong-Chul Kim: Gwangju Institute of Science and Technology
Yoon Jun Kim: Seoul National University College of Medicine
Yuri Cho: CHA University School of Medicine
Mi Sun Jin: Gwangju Institute of Science and Technology
Sung-Gyoo Park: Gwangju Institute of Science and Technology

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10200-5

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