宿主细胞膜上的唾液酸受体与一种特定病毒蛋白质之间的相互作用可作为天然抗体的标靶以阻断流感病毒传染，近日《自然—结构与分子生物学》杂志报道的这项发现为研究治疗药物如何模拟相同的相互作用提供了潜在可能。
Ian Wilson、James Crowe等人获取了3种不同中和抗体的X射线图，每种抗体都与H2N2病毒株中的病毒血凝素蛋白（HA）相结合。所有这3种抗体都嵌入到HA受体结合位点中的空洞里，其所使用的机制相同，并与一种在所有流感病毒株中存在的残基发生接触。
先前研究已认为唾液酸类似物可作为潜在的流感抑制剂，但研究结果收效甚微。结合之前的研究体系，这次研究为利用小型蛋白或小分子复合物开发新的抑制剂提供了新方向。（生物谷Bioon.com）
doi:10.1038/nsmb.2500
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A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin
Rui Xu, Jens C Krause, Ryan McBride, James C Paulson, James E Crowe Jr & Ian A Wilson
Influenza virus hemagglutinin (HA) mediates receptor binding and viral entry during influenza infection. The development of receptor analogs as viral-entry blockers has not been successful, which suggests that sialic acid may not be an ideal scaffold to obtain broad, potent HA inhibitors. Here, we report crystal structures of Fab fragments from three human antibodies that neutralize the 1957 pandemic H2N2 influenza virus in complex with H2 HA. All three antibodies use an aromatic residue to plug a conserved cavity in the HA receptor-binding site. Each antibody interacts with the absolutely conserved HA1 Trp153 at the cavity base through π-π stacking with the signature Phe54 of two VH1-69–encoded antibodies or a tyrosine from HCDR3 in the other antibody. This highly conserved interaction can be used as a starting point to design inhibitors targeting this conserved hydrophobic pocket in influenza viruses.
