Russell Rupert J, Kerry Philip S, Stevens David J, Steinhauer David A, Martin Stephen R, Gamblin Steven J, Skehel John J
Interdisciplinary Center for Human and Avian Influenza Research, School of Biology, University of St. Andrews, Fife KY16 9ST, United Kingdom.
Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17736-41. doi: 10.1073/pnas.0807142105. Epub 2008 Nov 12.
The influenza surface glycoprotein hemagglutinin (HA) is a potential target for antiviral drugs because of its key roles in the initial stages of infection: receptor binding and the fusion of virus and cell membranes. The structure of HA in complex with a known inhibitor of membrane fusion and virus infectivity, tert-butyl hydroquinone (TBHQ), shows that the inhibitor binds in a hydrophobic pocket formed at an interface between HA monomers. Occupation of this site by TBHQ stabilizes the neutral pH structure through intersubunit and intrasubunit interactions that presumably inhibit the conformational rearrangements required for membrane fusion. The nature of the binding site suggests routes for the chemical modification of TBHQ that could lead to the development of more potent inhibitors of membrane fusion and potential anti-influenza drugs.
流感病毒表面糖蛋白血凝素（HA）是抗病毒药物的潜在靶点，因为它在感染初期起着关键作用：受体结合以及病毒与细胞膜的融合。HA与一种已知的膜融合和病毒感染性抑制剂叔丁基对苯二酚（TBHQ）形成的复合物结构表明，该抑制剂结合在HA单体之间界面处形成的疏水口袋中。TBHQ占据该位点通过亚基间和亚基内相互作用稳定了中性pH结构，推测这些相互作用抑制了膜融合所需的构象重排。结合位点的性质为TBHQ的化学修饰提供了途径，这可能会导致开发出更有效的膜融合抑制剂和潜在的抗流感药物。
