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Putting a bull's-eye on the flu: Paper details influenza's structure for future drug targeting
Date:10/21/2010

Beating the flu has always been tough, but it has gotten even more difficult in recent years. Two of the four antiviral drugs used to treat a nasty case of the influenza A virus no longer work.

Fortunately, scientists at the National High Magnetic Field Laboratory and Institute of Molecular Biophysics at Florida State University and researchers at Brigham Young University in Utah are close to understanding why these drugs have become less effective and how new drugs might take their place. Their findings appear this week in the journal Science.

"Resistance to drugs is a fundamental problem that develops from their misuse, overuse and underuse," said Timothy A. Cross, the Earl Frieden Professor of Chemistry and Biochemistry at Florida State and director of the Magnet Lab's Nuclear Magnetic Resonance Program, as well as one of the Science article's senior authors. Compounding the problem is that "the development of new drugs to take their place is a decade-long process with infrequent success."

The two drugs no longer recommended by the U.S. Centers for Disease Control amantadine (brand names Symadine and Symmetrel) and rimantadine (Flumadine) have been used to fight the flu since 1969. For decades, they worked by preventing an essential protein function during viral infection of healthy cells. The protein, called the M2 channel, plays a key role in the virus' ability to reproduce. But the M2 channel mutated just enough to allow the virus to resist both drugs.

"Our work provides a blueprint on how protons are moved through a passageway inside the M2 channel," said Huan-Xiang Zhou, an FSU physics professor and the other senior co-author of the Science article. Interfering with that passageway is "an obvious route for drug development."

To study the M2 channel, researchers enlisted the help of one of the magnet lab's crown jewels: the 900-megahertz, nuclear magnetic resonance magnet. The 40-ton magnet was used
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Contact: Timothy A. Cross
cross@magnet.fsu.edu
850-644-0917
Florida State University
Source:Eurekalert  

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