lsothlafliudilne, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation

	lsothlafliudilne, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation
	Yang Li 1; Shi Liping 1; Chen Haijun 1; Tong Xiankun 1; Wang Guifeng 1; Zhang Yangming 1; Wang Weniong 1; Feng Churlian 1; He Peilan 1; Zhu Fenghua 1
刊名	Acta Pharmacologica Sinica
	2014
卷号	35 期号:3 页码:410
关键词	hepatitis B virus replication capsid assembly pregenomic RNA non-nucleoside compound isothiafludine lamivudine adefovir entecavir
ISSN号	1671-4083
英文摘要	Aim: To investigate the action of isothiafludine (NZ-4),a derivative of b/s-heterocycle tandem pairs from the natural product leucamide A, on the replication cycle of hepatitis B virus (HBV) in wtro and in vivo. Methods: HBV replication cycle was monitored in HepG2.2.15 cells using qPCR, qRT-PCR,and Southern and Northern blotting. HBV protein expression and capsid assembly were detected using Western blotting and native agarose gel electrophoresis analysis. The interactionof pregenomic RNA (pgRNA) and the core protein was investigated by RNA immunoprecipitation. To evaluate the anti-HBV effect of NZ-4 in vivo, DHBV-infected ducks were orally administered NZ-4 (25, 50 or 100 mg·kg~(-1)·d~(-1)) for 15 d. Results: NZ-4 suppressed intracellular HBV replication in HepG2.2.15 cells with an lC_(50) value of 1.33 IJmol/L,whereas the compound inhibited the cell viability with an lC_(50) value of 50.4 μmol/L. Furthermore, NZ-4 was active against the replication of various drug-resistant HBV mutants, including 3TC/ETV-dual-resistant and ADV-resistant HBV mutants. NZ-4 (5, 10,and 20 μmoI/L) concentration-dependently reduced the encapsidated HBV pgRNA, resulting in the assembly of replication-deficient capsids in HepG2.2.15 cells. Oral administration of NZ-4 dose-dependently inhibited DHBV DNA replication in the DHBV-infected ducks. Conclusior: NZ-4 inhibits HBV replication by interfering with the interaction between pgRNA and HBcAg in the capsid assembly process, thus increasing the replication-deficient HBV capsids. Such mechanism of action might provide a new therapeutic strategy to combat HBV infection.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/293713]
专题	中国科学院上海药物研究所
作者单位	1.中国科学院上海药物研究所 2.华中科技大学同济医学院
推荐引用方式 GB/T 7714	Yang Li,Shi Liping,Chen Haijun,et al. lsothlafliudilne, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation[J]. Acta Pharmacologica Sinica,2014,35(3):410.
APA	Yang Li.,Shi Liping.,Chen Haijun.,Tong Xiankun.,Wang Guifeng.,...&Jian Pingzuo.(2014).lsothlafliudilne, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation.Acta Pharmacologica Sinica,35(3),410.
MLA	Yang Li,et al."lsothlafliudilne, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation".Acta Pharmacologica Sinica 35.3(2014):410.