Structure-based design and biochemical evaluation of sulfanilamide derivatives as hepatitis B virus capsid assembly inhibitors

被引:11
作者
Cho, Min-Hyung [1 ]
Song, Jin-Su [2 ]
Kim, Hie-Joon [2 ]
Park, Sung-Gyoo [3 ,4 ]
Jung, Guhung [1 ]
机构
[1] Seoul Natl Univ, Dept Biol Sci, Seoul 151742, South Korea
[2] Seoul Natl Univ, Dept Chem, Seoul 151742, South Korea
[3] Gwangju Inst Sci & Technol, Sch Life Sci, Kwangju 500712, South Korea
[4] Gwangju Inst Sci & Technol, Bioimaging Ctr, Kwangju 500712, South Korea
基金
新加坡国家研究基金会;
关键词
Capsid assembly inhibition; hepatitis B virus; cp149; structure simulation; rational drug design; PROTEIN; PHOSPHORYLATION; FEATURES; MODELS; ZINC;
D O I
10.3109/14756366.2012.694879
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Virus capsid structure is essential in virion maturation and durability, so disrupting capsid assembly could be an effective way to reduce virion count and cure viral diseases. However, currently there is no known antiviral which affects capsid inhibition, and only a small number of assembly inhibitors were experimentally successful. In this present study, we aimed to find hepatitis B virus (HBV) capsid assembly inhibitor which binds to the HBV core protein and changes protein conformation. Several candidate molecules were found to bind to certain structure in core protein with high specificity. Furthermore, these molecules significantly changed the protein conformation and reduced assembly affinity of core protein, leading to decrease of the number of assembled capsid or virion, both in vitro and in vivo. In addition, prediction also suggests that improvements in inhibition efficiency could be possible by changing functional groups and ring structures.
引用
收藏
页码:916 / 925
页数:10
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