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Promising New Target in War Against Flu

Promising New Target in War Against Flu

Scientists at The University of Texas at Austin have discovered that a protein produced by the influenza A virus, which causes flu, can overcome one of our body's natural defense mechanisms. That makes this flu protein a potentially good target for antiviral drugs directed against the flu virus

Image credit: Pixabay, via Creative Commons CC0 license.

This isn't the first time Robert Krug and his team have identified promising targets for antiviral flu treatments. For example, the team's previous study from April 2014 announced the discovery of another countermeasure that influenza A uses to block the human immune response. Krug says this year's discovery is even more promising.

Better antiviral drugs could help the millions of people annually infected by flu, which kills up to 500,000 people worldwide each year.

When an influenza virus infects a human cell, it copies its genetic material using a viral enzyme that contains three proteins. In this latest study, the researchers discovered that a protein produced by human cells, called ZAPL, blocks this replication process by degrading two of the three viral proteins in this crucial enzyme. Unfortunately, the flu fights back with the third protein, which interferes with ZAPL.

The complicated dance between viral and host proteins indicates an ever-escalating evolutionary arms race.

"Right now, this third viral protein can knock off the other two from ZAPL and rescue the virus," says Krug, a professor in UT Austin's Department of Molecular Biosciences and corresponding author on the study in this week's Proceedings of the National Academy of Sciences. "When it's free to do its work, ZAPL destroys these two critical viral proteins. They're just gone."

The first author of the study is a graduate student, Chien-Hung Liu, whose PhD thesis consisted of this research.

Krug says that if researchers could find a drug that stops this third viral protein from inhibiting ZAPL, the body would be much better equipped to deal with flu. Krug and his team are now working to learn more about the problematic ZAPL-interfering protein, which would also provide key information for future drug development.

When the human protein ZAPL is free to do its work, it binds and degrades to the flu virus protein PB2 (top). But if the viral protein PB1 is present (bottom), it knocks PB2 off of ZAPL and rescues the virus from the host's immune attack. Credit: Robert Krug.
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Friday, 06 December 2019

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