Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California, USA.
Nat Struct Mol Biol. 2013 Mar;20(3):363-70. doi: 10.1038/nsmb.2500. Epub 2013 Feb 10.
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.
流感病毒血凝素（HA）在流感感染过程中介导受体结合和病毒进入。作为病毒进入抑制剂的受体类似物的开发并不成功，这表明唾液酸可能不是获得广泛、强效 HA 抑制剂的理想支架。在这里，我们报告了三种中和 1957 年大流行 H2N2 流感病毒的人源抗体 Fab 片段的晶体结构，这些抗体与 H2 HA 形成复合物。这三种抗体都使用芳香族残基来填充 HA 受体结合位点中的一个保守腔。每个抗体都通过与两个 VH1-69 编码抗体的特征性 Phe54 或另一个抗体的 HCDR3 中的酪氨酸进行 π-π 堆积，与空腔底部的绝对保守的 HA1 Trp153 相互作用。这种高度保守的相互作用可以作为设计针对流感病毒中这个保守疏水口袋的抑制剂的起点。
