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Protein's tail may be flu virus's achilles heel

HOUSTON, Dec. 6, 2006 -- Striking new research from Rice University and the University of Texas at Austin (UT) has revealed a potential new target that drug makers can use to attack several strains of influenza, including those that cause bird flu as well as the common variety that infects millions each flu season.

The research, published online today by Nature, offers tantalizing evidence of a potential drug target in a flu protein called nucleoprotein, or NP. NP plays a vital role in all strains of influenza A, including Hong Kong flu, Spanish flu and bird flu.

The target is NP's long, flexible tail. Biochemists at Rice and UT found that even minor changes to the tail prevented NP from fulfilling one of its roles linking together into structural columns that the virus uses to transmit copies of itself.

"There is a small binding pocket for the tail loop of the protein that appears to be a promising target for a new class of antiviral drugs," said lead researcher Jane Tao, assistant professor in biochemistry and cell biology. "We know from previous genetic studies that this tail loop is almost identical across strains of influenza A, so drugs that target the tail have a high potential of being effective against multiple strains, including the H5N1 strains. Such new antivirals are especially needed at the moment as some H5N1 viruses are resistant to the flu drug Tamiflu."

Tao's findings are based on a painstaking series for experiments that revealed the atomic structure of NP. The protein's structure was discerned via X-ray crystallography, a method that allows scientists to discern the three-dimensional placement of atoms in a crystal based upon the diffraction patterns of X-rays that pass through it.

Tao said it was a challenge to growing NP protein crystals. The method used was the hanging drop vapor diffusion method, which involves suspending a liquid droplet of concentrated protein solution on
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Contact: Jade Boyd
jadeboyd@rice.edu
713-348-6778
Rice University
6-Dec-2006


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