New Drugs Beat Old Flu: Antiviral agents counter deadly 1918 influenza

A greater killer than the First World War, the influenza virus that swept the globe from 1918 to 1919 took the lives of 20 million to 40 million people. After partially recreating that deadly virus, a research team has now shown that available flu drugs could probably prevent a new pandemic of the 1918 influenza strain or a similar flu.

OLD-STYLE MEDICINE. Emergency hospitals, such as this one in Kansas, dealt with the 1918 flu epidemic that killed more than 20 million people. National Museum of Health and Medicine, AFIP

In recent years, scientists studying tissue preserved since 1918 have pieced together several genes from this deadly influenza strain, also commonly known as the Spanish flu (SN: 3/22/97, p. 172: Virologists are investigating why that virus was so lethal compared with typical influenza strains, but its genes and the proteins they encode haven’t offered any obvious answer.

Christopher F. Basler of Mount Sinai School of Medicine in New York and his colleagues have now incorporated several genes from the 1918 flu into an influenza strain that has adapted to mice and typically kills the rodents. The introduced viral genes encode a surface protein called hemagglutinin (HA), an enzyme known as neuraminidase (NA), and two proteins dubbed M1 and M2.

The researchers expected that those genes would reduce the virulence of the mouse-adapted virus. Flu viruses isolated from people rarely prove lethal to rodents, and genes from human-adapted strains typically weaken rodent-influenza viruses.

Not so for the HA and NA genes of the 1918 flu. The engineered virus containing both of these genes readily killed mice, the scientists report in an upcoming issue of the Proceedings of the National Academy of Sciences. The HA and NA genes, when each was present alone, lowered virulence. This suggests that the specific combination of HA and NA may underlie the 1918 flu disaster. “In any influenza [strain], the HA and NA have to be compatible for the virus to grow well,” says Basler.

The researchers also tested whether the two recently approved classes of flu drugs combat pseudo-1918 viruses. Starting treatment with NA inhibitors before introducing the HA-NA engineered virus prevented 90 percent of the mice from dying, they found. And all mice infected with a flu strain carrying the 1918 gene for M2 survived when treated with M2 inhibitors, even if treatment began 6 hours after infection.

“The drugs appear to be effective against viruses with the 1918 genes,” says Basler.

In people, these antiviral drugs are more effective at preventing infections than at treating people already afflicted, notes Basler. Consequently, he says, public health officials would probably advocate precautionary use of the drugs if they foresaw a major influenza outbreak.

Basler notes that the mouse work was done in a facility especially designed for studying dangerous influenza strains. Virologists at the same facility study a 1997 flu strain that originated in Hong Kong chickens and sparked fears of a new worldwide epidemic (SN: 12/13/97, p. 372:

“Clearly, once you start putting multiple 1918 genes into a virus, concerns about safety increase,” says Basler. “There’s no guarantee a 1918-like virus couldn’t return, so it’s important to understand what was going on back then.”

Robert Krug of the University of Texas at Austin and other virologists have called for the global stockpiling of NA and M2 inhibitors to ward off a natural influenza pandemic or one started by terrorists. Still, he’s fearful the new study could offer a false sense of security, especially since viruses quickly develop resistance to drugs. “Hong Kong–like viruses are a bigger threat than the 1918 virus, and we need additional antivirals,” he says.


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