物理化学学报 >> 2017, Vol. 33 >> Issue (3): 633-641.doi: 10.3866/PKU.WHXB201612052

论文 上一篇    

禽流感病毒HA蛋白与人受体的分子对接

邓迎春,柳青,黄强*()   

  • 收稿日期:2016-10-28 发布日期:2017-03-07
  • 通讯作者: 黄强 E-mail:huangqiang@fudan.edu.cn
  • 基金资助:
    国家自然科学基金(91430112);国家自然科学基金(31671386);NSFC-广东联合基金(第二期)超级计算科学应用研究专项和国家超级计算广州中心支持资助项目

Molecular Docking of Human-Like Receptor to Hemagglutinins of Avian Influenza A Viruses

Ying-Chun DENG,Qing LIU,Qiang HUANG*()   

  • Received:2016-10-28 Published:2017-03-07
  • Contact: Qiang HUANG E-mail:huangqiang@fudan.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(91430112);the National Natural Science Foundation of China(31671386);Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund (the Second Phase), China

摘要:

血凝素(hemagglutinin,HA)是位于禽流感病毒表面的糖蛋白。在病毒感染过程中,HA与禽类宿主细胞表面受体结合,介导病毒膜与宿主核内体膜的融合,在传染过程中发挥关键作用。自然界中的禽流感病毒处于不断演化之中,其HA的禽受体结合位点常常发生氨基酸变异。因此,当HA变异体与人受体结合能力较强时,禽流感病毒往往会发生跨种传播而感染人。为预防禽流感的跨种传播,人们迫切需要发展大规模快速检测或预测HA变异体与人受体结合亲和力的方法,以评估各种新发禽流感病毒的跨种传播能力,提前筛选出有潜在危险的病毒株。针对此问题,本研究以H7N9亚型的HA蛋白H7为研究对象,发展了一种运用分子对接的计算方法,预测HA变异体与人受体的结合亲和力。该方法的计算结果表明,H7与人受体的结合亲和力普遍弱于有较强传染人能力的H1,说明H7N9亚型病毒的跨种传播能力普遍较弱;但是,计算分析也揭示,部分新发的H7N9毒株的HA有强的人受体结合亲和力,提示在自然演化过程中,H7N9病毒有可能演化出具有较强的感染人能力的新毒株,这与2013年禽流感疫情的实际发生情况相一致。因此,本文所发展的计算方法可用于快速预测新发禽流感病毒HA与人受体的结合亲和力,为新发禽流感病毒的跨种传播风险评估提供理论依据。

关键词: 禽流感病毒, 跨种传播, 受体结合特异性, 分子对接, 结合自由能

Abstract:

Hemagglutinin (HA) is a glycoprotein located on the surface of the avian influenza A viruses. HA plays a key role in the infection process, binding to receptors on the host cell surface and mediating the fusion between viral and host endosomal membranes. In nature, influenza A virus undergoes continuous variation, particularly the amino acid sequence at the receptor binding site of HA. When the binding ability of HA variants towards human receptors becomes strong, influenza A virus can infect humans. To prevent the influenza A virus from infecting humans, proper assessments of the infectious risk posed are urgently needed. Screening of high risk virus strains by analyzing the binding ability of HA variants for human receptors through a high-throughput method would be particularly useful. In this study, we used H7 (a subtype of HA) as a subject and developed a molecular docking based theoretical calculation method to evaluate the affinity of HA variants for human receptors. The results showed that the binding affinity of H7 for human receptors is lower than that of H1, which shows a strong ability to infect humans. This result suggests that strains of the H7 subtype are generally weakly infectious in humans. Nevertheless, the calculation results also showed that some newly-found virus strains of the H7N9 subtype have a high binding affinity for human receptors, suggesting that the H7N9 subtype might include strains with a high risk for infecting humans. These results are consistent with the actual occurrence of the 2013 H7N9 epidemic. Our method may be used to rapidly predict the affinity of HA for human receptors and provides a theoretical basis for the risk assessment of the infectiousness of influenza A virus toward humans.

Key words: Influenza A virus, Interspecies transmission, Receptor-specificity, Molecular docking, Binding free energy

MSC2000: 

  • O641