Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly.
Nat Commun
; 10(1): 2184, 2019 05 16.
Article
em En
| MEDLINE
| ID: mdl-31097716
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Vírus da Hepatite B
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Montagem de Vírus
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Hepatite B Crônica
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Ciclopirox
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2019
Tipo de documento:
Article