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Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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, 2019. "Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10200-5
    DOI: 10.1038/s41467-019-10200-5
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