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See Inside November 2010

Finding a Killer's Achilles' Heel: Clues from a Pandemic

The 1918 flu genome may help fight future outbreaks



Photo Researchers, Inc.

It has been five years since a team of scientists resurrected the 1918 influenza virus from the lungs of a long-frozen victim. At the time, the Jurassic Park–like feat was both widely celebrated and sharply criticized. Opponents worried about the risk of an accidental (or intentional) release of the revived killer, which claimed between 50 million and 100 million lives in about 15 months and has been dubbed the worst plague in human history. Proponents insisted that the insights gained from a fully reconstructed virus would be instrumental in fighting the next pandemic.

A paper published in the November issue of the journal Microbe cites a potential new drug target, among other findings, as evidence that the risk was not taken in vain. Terrence Tumpey of the Centers for Disease Control and Prevention and his colleagues have closed in on a protein called PB1 that enables the virus to copy itself. When researchers substituted the PB1 protein in a normal flu virus with the 1918 version of that same protein, the normal virus morphed into a superkiller: it replicated and spread through its rodent host eight times faster, killing more mice as a result. It turns out that all 20th-century pandemic viruses, among them the 2009 swine flu, have avian flu PB1 genes. Most seasonal flu viruses have human flu PB1 genes.

Scientists are now working to develop new drugs that target PB1. Small molecules that bind to the protein’s receptors could prevent the virus from replicating and might greatly reduce virulence. The need for new antiflu drugs is increasingly urgent, as several recent flu strains, including the swine flu, have developed resistance to currently available treatments such as Tami­flu. When combined with the older antivirals, PB1-targeted drugs could drastically reduce the spread of resistance, making the approach of the annual flu season a little less worrisome for everyone.

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