New Drugs May Fight Deadliest Flu Virus

Mouse study suggests they'd work against 1918-like pandemic

TUESDAY, Sept. 24, 2002 (HealthDayNews) -- If the whopper flu virus of 1918 ever resurfaces, doctors may be well-equipped to deal with the outbreak.

So suggests a new study, which found that new drugs that attack flu virus can protect mice from dying when infected with rodent flu studded with genes to make it more vicious. Versions of the drugs, called neuraminidase inhibitors, are already on the market to treat and prevent garden-variety flu.

The 1918 "Spanish" flu pandemic killed more than 21 million people worldwide, and at least 500,000 in the United States alone, making it the most devastating outbreak on record. Conventional influenza, by comparison, kills 20,000 people a year in this country.

Although scientists have made strides toward understanding the genetics of the pandemic microbe and why it was so deadly, many aspects of its virulence remain a mystery. So the prospect that the 1918 strain could re-emerge -- either by chance or an act of biological warfare -- has some scientists in a theoretical fret.

Yet the new study, reported this week in the Proceedings of the National Academy of Sciences, suggests a return of the 1918 flu might be stiff-armed by the combination of vaccination, neuraminidase inhibitors, and other antiviral drugs.

A research team led by Christopher F. Basler of Mount Sinai School of Medicine in New York City tested three of these compounds on mouse flu virus genetically engineered to mimic the old killer. Scientists don't have samples of the 1918 pathogen. However, Basler's group built three genes, encoding for four proteins, thought to belong to the microbe. They then stitched these genes into the genome of the mouse flu, which is itself quite deadly to the animals.

Left alone, all the mice would die once infected with the virus. Basler and his colleagues found, however, that roughly 90 percent of animals given the drug oseltamivir -- a neuraminidase inhibitor sold as Tamiflu by Roche Pharmaceuticals -- for a day before and six days after infection survived. A similar compound, zanamivir, or Relenza, made by GlaxoSmithKline, was effective in a lab dish, but they didn't test it in live mice.

Treatment during the illness with two other drugs, called M2 ion channel inhibitors -- amantadine and rimantadine -- saved all that received the medication. Although the rodents lost weight while sick, they shed fewer grams than untreated animals.

"If you don't give the drugs. the mice become ill and they die. If you do give them, you protect them from death," Basler says.

Scientists have now mapped four of the eight bundles of genetic material that make up the 1918 flu. Basler and his colleagues think they might have a lead with two of the genes they reconstructed for the latest study -- hemagglutinin (HA) and neuraminidase (NA).

The first gene helps the virus latch onto host cells, while the second lets it release new copies that can infect other tissue. "Maybe something interesting is going on with these two genes in terms of making [the strain] so deadly," Basler says. "But at the moment it's still very unclear."

A third gene, called matrix (M), may also prove helpful, says Terrence Tumpey, a microbiologist at the U.S. Department of Agriculture's Southeast Poultry Research Laboratory, in Athens, Ga., and a co-author of the study.

Tumpey cautions it's difficult to apply the work to humans, or to say that scientists have indeed succeeded in simulating the 1918 flu strain.

"You have to consider that these studies were done in mice, which may not correlate" to people, he says. In addition, "we're only looking at some of the genes and not all of them."

What To Do

For more on the 1918 flu pandemic, try this site from PBS. For more on the flu that's circulating these days, try the Centers for Disease Control and Prevention.

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