Rensselaer Research Review Summer 2009
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New Flu Treatment Targets Both the H and N Portions of the Disease
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Robert Linhardt
Robert Linhardt, the Ann and John H. Broadbent Jr. ’59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer
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Promising new research announced by Rensselaer Polytechnic Institute could provide an entirely new tool to combat the flu. The discovery is a one-two punch against the illness that targets the illness on two fronts, going one critical step further than any currently available flu drug.

“We have been fortunate with H1N1 (Swine Flu) because it has been responding well to available drugs. But if the virus mutates substantially, the currently available drugs might be ineffective because they only target one portion of the virus,” said Robert Linhardt, the Ann and John H. Broadbent Jr. ’59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer. “By targeting both portions of the virus, the H and the N, we can interfere with both the initial attachment to the cell that is being infected and the release of the budding virus from the cell that has been affected.”

The findings of the team, which have broad implications for future flu drugs, were featured on the cover of the June edition of European Journal of Organic Chemistry.

Targeting Both Hemagglutinin and Neuraminidase

The influenza A virus is classified based on the form of two of its outer proteins, hemagglutinin (H) and neuraminidase (N). Each classification — for example H5NI “bird flu” or H1N1 “swine flu” — represents a different mutation of hemagglutinin and neuraminidase or H and N.

Flu drugs currently on the market target only the neuraminidase proteins, and disrupt the ability of the virus to escape an infected cell and move elsewhere to infect other healthy cells. The new process developed by Linhardt is already showing strong binding potential to hemagglutinin, which binds to sialic acid on the surface of a healthy cell, allowing the virus to enter the cell.

“We are seeing promising preliminary results that the chemistry of this approach will be effective in blocking the hemagglutinin portion of the disease that is currently not targeted by any drug on the market,” he said.

In addition, Linhardt and his team have shown their compound to be just as effective at targeting neuraminidase as the most popular drugs on the market, according to Linhardt.

The approach can also be modified to specifically target the neuraminidase or the hemagglutinin, or both, depending on the type of mutation that is present in the current version of the flu, according to Linhardt.

In the next steps of his research, Linhardt will look at how their compounds bind to hemagglutinin, and he will test the ability to block the virus first in cell cultures and then in infected animal models.

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“New Flu Treatment Targets
Both the H and N Portions of the Disease”
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