Biocatalysis and Metabolic Engineering

What happens if the next big influenza mutation proves resistant to the available anti-viral drugs? This question presented itself to scientists and health officials in May at the World Health Assembly in Geneva, Switzerland, as they continued to do battle with H1N1 (swine flu) and prepared for the next iteration of the ever-changing flu virus. Promising new research announced by Rensselaer could provide a new tool to combat the flu. The discovery is a one-two punch that targets the illness on two fronts, going one step further than any currently available flu drug.

“We have been fortunate with H1N1 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,” says Robert Linhardt, the Ann and John H. Broadbent Jr. ’59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering. “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 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 says. 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.

“We are several steps away from a new drug,” Linhardt says, “but this technique is allowing us to move very quickly in creating and testing these compounds.”