BAY41-4109对乙肝病毒衣壳组装的影响

Bay 41-4109 interacts with HBV capsid/capsid proteins and affects the assembly of HBV

乙肝病毒衣壳蛋白成功组装成衣壳二十面体的过程是病毒前基因组RNA逆转录形成成熟DNA的必要步骤。衣壳结构的轻微改变或破坏能对病毒子代传播产生巨大影响。应用透射电子显微镜研究发现小分子抗病毒化合物(heteroaryldihydropyrimidine,HAP)BAY41-4109在与衣壳蛋白二聚体摩尔浓度比达到1∶2时,能干扰乙肝病毒衣壳蛋白组装成衣壳二十面体。在BAY41-4109的作用下,衣壳蛋白发生错误组装,形成不规则球体、平面片状结构和管状结构。应用图像处理技术对管状结构进行分析,发现它是衣壳蛋白重新装配形成的具有螺旋对称性的规则组装体,衣壳蛋白按六角晶格方式排列,其最小组成单位是衣壳蛋白的二聚体。

Hepatitis B Virus （HBV） is an enveloped DNA virus with an icosahedral core （capsid）. Assembly of the icosahedral core capsid is required for reverse transcription of the RNA pregenome to the mature DNA form. Modest mutations of the capsid protein （Cp） can have dramatic effects on the viability of progeny virus. The effect of a heteroaryldihydropyrimidine （HAP） antiviral compound, BAY 41-4109, on HBV capsid assembly and preformed HBV capsid was investigated. The results show that for both capsid assembly and preformed capsid, a stoichiometry of two Cp dimers per BAY 41-4109 drug molecule （[ BAY] ： [ Cp Dimer] = 1：2） or above can misdireetly assembly and lead to aberrant structures, including irregular spheres, sheets and tubes. Image processing of the tubular structures reveals that capsid proteins are rearranged into a hexagonal lattice with the Cp dimer as the assembly unit.