Novel fluoronucleoside analog NCC inhibits lamivudine-resistant hepatitis B virus in a hepatocyte model
Braz. j. infect. dis
; 22(6): 477-486, Nov.-Dec. 2018. tab, graf
Artigo
em Inglês
| LILACS
| ID: biblio-984016
Biblioteca responsável:
BR1.1
ABSTRACT
ABSTRACT Antiviral drug resistance is the most important factor contributing to treatment failure using nucleos(t)ide analogs such as lamivudine for chronic infection with hepatitis B virus (HBV). Development of a system supporting efficient replication of clinically resistant HBV strains is imperative, and new antiviral drugs are needed urgently to prevent selection of drug-resistant HBV mutants. A novel fluorinated cytidine analog, NCC (N-cyclopropyl-4′-azido-2′-deoxy-2′-fluoro-β-d-cytidine), was recently shown to strongly inhibit human HBV in vitro and in vivo. This study was designed to evaluate the antiviral activity of NCC against lamivudine-resistant HBV. We generated a stable cell line encoding the major pattern of lamivudine-resistant mutations rtL180M/M204V and designated it "HepG2.RL1". Immuno-transmission electron microscopic examination and enzyme-linked immunosorbent assay were used to detect secretion of HBV-specific particles and antigens. Quantification of extracellular DNA and intracellular DNA of HepG2.RL1 cells by quantitative real-time polymerase chain reaction revealed >625-fold and >5556-fold increases in the 50% inhibitory concentration of lamivudine, respectively, compared with that for the wild-type virus. The results showed that NCC inhibited DNA replication and HBeAg production in wild-type or lamivudine-resistant HBV in a dose-dependent manner. In conclusion, screening for antiviral compounds active against lamivudine-resistant HBV can be carried out with relative ease using hepG2.RL1 cells. NCC is a potential antiviral agent against wild-type HBV and clinical lamivudine-resistant HBV and deserves evaluation for the treatment of HBV infection.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
LILACS
Assunto principal:
Antivirais
/
Replicação Viral
/
Vírus da Hepatite B
/
Lamivudina
/
Citidina
Tipo de estudo:
Estudo prognóstico
Limite:
Feminino
/
Humanos
Idioma:
Inglês
Revista:
Braz. j. infect. dis
Assunto da revista:
Doenças Transmissíveis
Ano de publicação:
2018
Tipo de documento:
Artigo
País de afiliação:
China
Instituição/País de afiliação:
The First Affiliated Hospital of Zhengzhou University/CN