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New flu drugs possible, but years away

Influenza viruses are quickly evolving resistance to the few drugs on the market that fight them, but there are weaknesses that could be exploited, experts told a conference on Tuesday.
/ Source: Reuters

Influenza viruses are quickly evolving resistance to the few drugs on the market that fight them, but there are weaknesses that could be exploited, experts told a conference on Tuesday.

Flu specialists say the need for better flu-fighting drugs has always been clear. Ordinary, seasonal influenza kills 250,000 to 500,000 people globally every year.

But the threat of a pandemic of H5N1 avian influenza, or any other kind of new virus, makes the need even more urgent.

Dr. Robert Krug, of the University of Texas at Austin, told a meeting of global flu experts in Toronto that his team has identified a good potential drug target, although he said it could take years to develop the drug.

It is a protein that the virus forces cells to make after it infects them. Because this protein is not something the virus itself makes, it does not appear to mutate like viral proteins do, Krug told reporters.

The protein is called NS 1 for nonstructural protein. When the influenza virus infects a cell, it hijacks the cell’s functions and forces it to become a virus factory.

The virus makes the cell produce NS 1, which disables the cell’s chemical defenses.

“If you can stop the NS 1 protein from doing this, the cell’s antiviral response, which is making interferon messages, is restored. And you thereby inhibit the virus,” Krug said.

Four drugs are on the market to treat flu but the older two are already so useless that they are no longer recommended.

“In the past, the market for flu antivirals was terrible and pharmaceutical companies weren’t particularly interested,” Krug said.

The resurgence in 2003 of H5N1, which has killed 191 out of 313 people infected, changed that. The virus mostly infects birds but it has spread out of Asia, into parts of Europe and Africa.

Stocking up
Countries have been stocking up on the antiviral drugs Tamiflu, invented by Gilead Sciences and Roche AG and a similar drug, Relenza, invented by Australia’s Biota and sold by GlaxoSmithKline.

“Now they are making a lot of money and there is more interest,” Krug said. “They’ll be interested when we have a good hit. They are not interested in funding us now.”

Krug said it would be years before anyone could make a drug that affected the NS 1 protein, and so government funding of the work is essential.

In the meantime it will be important to watch H5N1 to make sure it remains a virus that infects mostly birds.

A new test can tell doctors quickly if a virus has developed the ability to easily infect people -- offering a way to monitor the H5N1 virus for the changes it would need to spark a pandemic, the researchers said.

James Paulson of The Scripps Research Institute in La Jolla, Calif., said a test his team developed in 2004 was used earlier this year to show that it took only two small mutations to turn the 1918 influenza virus, which killed 50 million people or more, into its killer form.

This test, which checks for the docking points on cells that are used by the virus, consists of a single glass slide, Paulson said. “It could be used for surveillance,” he said.

This is key because it currently can take weeks to do the genetic testing needed to see whether a virus has mutated — weeks during which a newly mutated strain could escape into the population and start an outbreak.