Designing an irresistible flu drug

Memphis, Tennessee, March 14, 2016

Influenza

The flu virus is a wily beast. Rapid changes in its genes make vaccines less effective, or help the virus resist common anti-flu medications.

New medications are needed to combat drug resistance, treat infected individuals and stop flu outbreaks before they spread. A research study from St. Jude has found promise in a new class of anti-influenza drugs that could form the basis of powerful new treatments.

L-742,001, an example of the new type of drug, gums up a bit of viral machinery that the flu virus uses to reproduce. The researchers found that even when grown for generations in the presence of this drug, the flu virus did not develop resistance.

"This finding is really an encouraging sign that under natural conditions the virus may not readily become resistant to this class of drug," said Richard Webby, PhD, of St. Jude Infectious Diseases.

To explore whether resistance could ever develop, the researchers gave evolution a shove by artificially changing the virus’s genetic material. They found that resistance to L-742,001 could develop via changes to a specific "pocket" in the viral machinery.

The discovery may spark the development of even better drugs.

"We already have molecules that bind much, much better than L-742,001, and stay away from one of the pockets that could evolve resistance," said Stephen White, DPhil, of St. Jude Structural Biology. "And these findings give us more insight into designing drugs that avoid that region."

The findings were published in the Proceedings of the National Academy of Sciences (PNAS).

Read the news release.

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