Structure of Neuraminidase N1 Complexed with Tamiflu
by Eric Martz (see also Lesson Plan)

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Background

1. Two molecules on the influenza virus surface, critical to its spread, are hemagglutinin H and neuraminidase N.
   
   
2. H and N come in two major groups and various subtypes, such as H1N1, H2N2, or H5N1. H5N1 (bird flu) is perceived as a pandemic threat.
   
   
3. H1N1 killed over 25,000,000 people within six months in 1918. Death often occurred within one day of the first symptoms. One in five suffered from the disease.
   
   
4. Developed nations are stockpiling anti-flu drugs such as Tamiflu, costing billions of dollars.
   
   
5. More:
   1. Search WikiPedia for "pandemic" and "spanish flu".
   2. Laurie Garrett wrote an authoritative overview of economic and political factors.
   3. Search Nature for H5N1 and Tamiflu.

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New Findings



"The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design", Russell et al., Nature 443:45 (September 7, 2006): on-campus   off-campus



1. Tamiflu and Relenza were designed to fit N2/N9. New structures of N1 reveal that one loop (147-152) is "out of place" for binding drug.
   
   
2. Thus it is surprising that these existing drugs work on avian flu N1.
   
   
3. But upon binding Tamiflu, the misplaced loop is pulled into drug contact, a case of "induced fit".
   
   
4. A cavity in N1 (absent in N2/N9) adjacent to bound drug is a novel potential drug target.
   
   
5. To visualize the above structural features in interactive 3D, see the Lesson Plan.