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
Artículo
en Inglés
| LILACS
| ID: biblio-984016
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:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
Antivirales
/
Replicación Viral
/
Virus de la Hepatitis B
/
Lamivudine
/
Citidina
Tipo de estudio:
Estudio pronóstico
Límite:
Femenino
/
Humanos
Idioma:
Inglés
Revista:
Braz. j. infect. dis
Asunto de la revista:
Enfermedades Transmisibles
Año:
2018
Tipo del documento:
Artículo
País de afiliación:
China
Institución/País de afiliación:
The First Affiliated Hospital of Zhengzhou University/CN
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