Flu-drug flap

Disagreement over how older influenza drugs stop the virus is stymieing efforts to find new compounds

Elie Dolgin
Nov 9, 2009
A scientific spat over how drugs affect the structure of an influenza channel could be imperiling the development of new drugs targeting seasonal and pandemic flu viruses such as the H1N1 swine flu.
DeGrado's M2, complexed with amantadine
In the fall of 2007, the scientific advisory board of Influmedix, a Radnor, PA-based biotech company aimed at developing novel anti-flu medications, convened a conference call to discuss an important flu protein, a proton channel called M2. Two different researchers associated with the company had just cracked the proton channel's atomic-scale structure, but the two then-unpublished structural models came to strikingly different conclusions about how two flu drugs targeted this channel.Influmedix founder linkurl:William DeGrado;http://degrado.med.upenn.edu/ of the University of Pennsylvania in Philadelphia, thought that the drugs amantadine and rimantadine prevented the channel from opening directly. Alternatively, scientific advisor linkurl:James Chou;http://chou.med.harvard.edu/contacts.htm of Harvard Medical School in Boston, Massachusetts, had evidence that the drugs bound...
Chou's M2, complexed with rimantadine
Top image credit: PDB ID: 3C9J/ A.L. Stouffer, R. Acharya, D. Salom, A.S. Levine, L.D. Costanzo, C.S. Soto, V. Tereshko, V. Nanda, S. Stayrook, W.F. DeGrado, Structural basis for the function and inhibition of an influenza virus proton channel, Nature 451: 596-600 (2008) Bottom image credit: PDB ID: 2RLF/ J.R. Schnell, J.J. Chou, Structure and mechanism of the M2 proton channel of influenza A virus, Nature 451: 591-595 (2008)

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