Saturday, August 26, 2006

New Weakness in Avian Flu Virus Found

New Weakness in Avian Flu Virus Found
08.16.06, 12:00 AM ET

WEDNESDAY, Aug. 16 (HealthDay News) -- British researchers have identified a feature of the avian flu virus that could be a target for new drugs.

"This points the way to the development, in the future, of other types of drugs," said Dr. Pascal James Imperato, distinguished service professor and chairman of the department of preventive medicine and community health at State University of New York Downstate Medical Center in New York City. "The results of the research do not nullify the effectiveness of current drugs, but simply show that there may be a possibility of developing new ones in the future."

Imperato was not involved in the research, which was published online Aug. 16 in Nature.

Any new drug development is not going to happen right away, however.

"Given the long time period that it takes in research and development of such drugs, and then FDA approval, I don't see that occurring probably for several years," Imperato added. "There's no immediate benefit."

On the other hand, once drugs are developed, they could be applied to other viruses as well.

Health officials across the globe have worried that the bird flu virus that has infected 238 people and killed 139 worldwide might mutate, possibly in tandem with a more common flu virus, unleashing a new type of flu virus that could prove even more deadly because people's immune systems would not be able to fend off the disease.

Different nations have been stockpiling the drugs oseltamivir (Tamiflu) and zanamivir (Relenza) should the current H5N1 bird flu mutate and become able to infect humans.

Both drugs inhibit the enzyme neuraminidase (the "N" in "H5N1"), found on the surface of the avian flu virus, but they only block the N2 and N9 versions.

"Those drugs were designed using the structure from one group of neuraminidases and, it turns out, genetically, there's another group," said John Skehel, senior author of the study and director of the National Institute of Medical Research in London. "The first group contains five neuraminidases, and the second group contains four."

"What we've done is determine the structure of three of those four, which hadn't been done before and, it turns out, they show some structural differences from the group that was used to develop Tamiflu and Relenza," he continued. "The major difference is the presence of a cavity next to the active site of the enzyme. In this group, the cavity is a constant feature."

This suggests that it may be possible to design or identify other compounds that would block neuraminidase activity.

"Relenza and Tamiflu work, so the idea is that this difference in structure might be used to develop new drugs which would block the neuraminidase just in this group," Skehel explained. "It may also well be that they block activity in both groups."

And it may block activity in viruses as well.

Skehel's group is currently working with pharmaceutical interests to find or develop new drugs. It's possible that new drugs might work in tandem with Tamiflu and Relenza to overcome resistance to those agents. "It would be a combination therapy like you have in HIV," Skehel explained.

Few would deny the need for new weapons against avian flu, but a human pandemic may not loom quite as large as it once appeared.

When government researchers recently tried to combine the deadly H5N1 strain of bird flu with a common strain of flu that infects humans, they were unable to produce a strain that could be transmitted easily. This indicates that the road to easily transmissible bird flu is more complicated than once thought.

Also, Bloomberg News recently reported that two Michigan swans infected with bird flu don't have the lethal form spreading elsewhere.

More information

Visit the U.S. Centers for Disease Control and Prevention for more on bird flu.

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