| Registro completo |
| Provedor de dados: |
BJID
|
| País: |
Brazil
|
| Título: |
Novel fluoronucleoside analog NCC inhibits lamivudine-resistant hepatitis B virus in a hepatocyte model
|
| Autores: |
Zhang,Jingmin
Wang,Yafeng
Peng,Youmei
Qin,Chongzhen
Liu,Yixian
Li,Jingjing
Jiang,Jinhua
Zhou,Yubing
Chang,Junbiao
Wang,Qingduan
|
| Data: |
2018-11-01
|
| Ano: |
2018
|
| Palavras-chave: |
N-cyclopropyl-4′-azido-2′-deoxy-2′-fluoro-β-D- cytidine
Hepatitis B virus
HepG2.RL1 cells
Lamivudine-resistant
RtL180M/M204V
|
| Resumo: |
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.
|
| Tipo: |
Info:eu-repo/semantics/article
|
| Idioma: |
Inglês
|
| Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702018000600477
|
| Editor: |
Brazilian Society of Infectious Diseases
|
| Relação: |
10.1016/j.bjid.2018.11.005
|
| Formato: |
text/html
|
| Fonte: |
Brazilian Journal of Infectious Diseases v.22 n.6 2018
|
| Direitos: |
info:eu-repo/semantics/openAccess
|
