宿主細(xì)胞膜上的唾液酸受體與一種特定病毒蛋白質(zhì)之間的相互作用可作為天然抗體的標(biāo)靶以阻斷流感病毒傳染，近日《自然—結(jié)構(gòu)與分子生物學(xué)》雜志報(bào)道的這項(xiàng)發(fā)現(xiàn)為研究治療藥物如何模擬相同的相互作用提供了潛在可能,。
Ian Wilson、James Crowe等人獲取了3種不同中和抗體的X射線圖,，每種抗體都與H2N2病毒株中的病毒血凝素蛋白（HA）相結(jié)合。所有這3種抗體都嵌入到HA受體結(jié)合位點(diǎn)中的空洞里,，其所使用的機(jī)制相同,，并與一種在所有流感病毒株中存在的殘基發(fā)生接觸,。
先前研究已認(rèn)為唾液酸類似物可作為潛在的流感抑制劑，但研究結(jié)果收效甚微,。結(jié)合之前的研究體系,，這次研究為利用小型蛋白或小分子復(fù)合物開發(fā)新的抑制劑提供了新方向。（生物谷Bioon.com）
doi:10.1038/nsmb.2500
PMC:
PMID:
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.
