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To stop flu infection, target host enzymes

Anne Harbig seeks to develop targeted treatments that prevent influenza viruses from entering potential host cells. For a flu infection to begin, the virus must have its surface protein called hemagglutinin cleaved by host enzymes known as proteases.

"A protease is a protein, an enzyme, that cleaves other proteins at specific sites," Harbig explained.

Because the virus cannot enter a cell without a protease present, Harbig and her colleagues are identifying proteases involved in activating certain flu strains so they can develop drugs that can block them.

Harbig used RNA sequencing to search for any segments of mRNA coding for proteases found in the lower respiratory system of mice. Once she identified an array of lung proteases, each one was tested individually for its ability to split apart the hemagglutinin on the surface of influenza B viruses. The proteases that were able to do so were narrowed down further to four candidates that activated influenza B infection in mouse cells.

"The idea is, if we know the protease that activates our virus, we can use protease inhibitors to prevent infection," Harbig said. "If we know all the proteases involved, we can test the inhibitors in murine models, in vivo, and if they work there, then maybe later [we can test them] in human studies."

Harbig has earned her Ph.D. and is continuing to work on the project, hoping to see it reach human clinical trials.