6J10

Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly

Summary for 6J10

• Entry DOI: 10.2210/pdb6j10/pdb
• Descriptor: Capsid protein, 6-cyclohexyl-4-methyl-1-oxidanyl-pyridin-2-one (3 entities in total)
• Functional Keywords: hepatitis b virus, ciclopirox, capsid assembly inhibitor, viral protein
• Biological source: Hepatitis B virus genotype D subtype adw (HBV)
• Total number of polymer chains: 6
• Total formula weight: 100774.18

Authors

Park, S.,Jin, M.S.,Cho, Y.,Kang, J.,Kim, S.,Park, M.,Park, H.,Kim, J.,Park, S.,Hwang, J.,Kim, Y.,Kim, Y.J. (deposition date: 2018-12-27, release date: 2019-04-17, Last modification date: 2024-10-23)

Primary citation

Kang, J.A.,Kim, S.,Park, M.,Park, H.J.,Kim, J.H.,Park, S.,Hwang, J.R.,Kim, Y.C.,Jun Kim, Y.,Cho, Y.,Sun Jin, M.,Park, S.G.
Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly.
Nat Commun, 10:2184-2184, 2019

PubMed 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.

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)