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516686 
Journal Article 
Structure of influenza hemagglutinin in complex with an inhibitor of membrane fusion 
Russell, RJ; Kerry, PS; Stevens, DJ; Steinhauer, DA; Martin, SR; Gamblin, SJ; Skehel, JJ 
2008 
1 
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
EISSN: 1091-6490 
105 
46 
17736-17741 
English 
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. 
crystallography; drug design; conformational-change; receptor-binding; a viruses; ph; oseltamivir; amantadine; neuraminidase; glycoprotein; infectivity; emergence