Wang Jing-Fang, Wei Dong-Qing, Chou Kuo-Chen
College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240, China.
Biochem Biophys Res Commun. 2009 Oct 16;388(2):413-7. doi: 10.1016/j.bbrc.2009.08.026. Epub 2009 Aug 8.
The M2 proton channel is one of indispensable components for the influenza A virus that plays a vital role in its life cycle and hence is an important target for drug design against the virus. In view of this, the three-dimensional structure of the H1N1-M2 channel was developed based on the primary sequence taken from a patient recently infected by the H1N1 (swine flu) virus. With an explicit water-membrane environment, molecular docking studies were performed for amantadine and rimantadine, the two commercial drugs generally used to treat influenza A infection. It was found that their binding affinity to the H1N1-M2 channel is significantly lower than that to the H5N1-M2 channel, fully consistent with the recent report that the H1N1 swine virus was resistant to the two drugs. The findings and the relevant analysis reported here might provide useful structural insights for developing effective drugs against the new swine flu virus.
M2质子通道是甲型流感病毒不可或缺的组成部分之一，在其生命周期中起着至关重要的作用，因此是抗该病毒药物设计的重要靶点。鉴于此，基于从一名近期感染H1N1（猪流感）病毒的患者身上获取的一级序列，构建了H1N1-M2通道的三维结构。在明确的水-膜环境下，对金刚烷胺和金刚乙胺这两种通常用于治疗甲型流感感染的商业药物进行了分子对接研究。结果发现，它们与H1N1-M2通道的结合亲和力显著低于与H5N1-M2通道的结合亲和力，这与近期关于H1N1猪病毒对这两种药物耐药的报道完全一致。本文报道的这些发现及相关分析可能为开发抗新型猪流感病毒的有效药物提供有用的结构见解。
