Stopping the flu virus: BYU research getting close

In the near future there will be more effective flu-fighting drugs

"Washing your hands is still the best defense against the flu," said Dr. David Busath, professor of physiology and developmental biology at BYU. "However, a team of researchers at BYU have been working hard to find a drug that could stop the flu, and we are getting closer."

The standard flu virus is dangerous because it has the uncanny ability to mutate. These mutations allow it to become resistant to drugs and vaccines. "There is always a threat for new virus strains," said Dr. Busath. "Viruses are classified as threats based on two criteria: the first is how lethal they are and the second is how contagious they are."

BYU biophysicist David Busath, coauthor of new science paper on the flu virus, leads a team at BYU testing drugs against flu.
BYU biophysicist David Busath, coauthor of new science paper on the flu virus, leads a team at BYU testing drugs against flu. Photo: Courtesy BYU

Here are a few examples of these two factors for the swine flu, Asian bird flu, seasonal flu and 1918 Spanish flu.

H1N1 (Swine flu): Considered highly contagious but not very lethal. In 2009 it killed about 10,000 people compared to 30,000 for the standard flu. Media attention began to taper off when the strain was considered less lethal than expected.

H5N1 (Asian bird flu): Considered very lethal but not very contagious. About 60 percent of those infected with bird flu die. According to 2011 World Health Organization data, only 306 humans have died from the bird flu H5N1 in 12 countries.

H3N2 (Seasonal flu): Highly contagious strain of the flu but not very deadly. The CDC reports that there were about 36,000 deaths in 2011 from seasonal flu. Vaccines are prepared every year to prevent flu.

1918 Spanish flu: Considered to be both lethal and highly contagious. According to a 2006 article by J. Morens Taubenberger from the CDC, one-third of the world's population was infected and 10 to 20 percent of those infected died (50 to 100 million). This type of flu is the model for the 2011 film "Contagion."

In the 1960s, two drugs were discovered to be effective at stopping the flu virus, amantadine and rimantadine. The drugs work by blocking a key channel of virus reproduction called the M2 channel, which must function correctly for the viral genes to be released into the healthy cell. Block the channel and the virus can't reproduce. However, the flu virus can mutate and drugs quickly become ineffective. That's what happened to amantadine and rimantadine. Dr. Busath said, "Today, 99 percent of the human flu strains in the world are immune to these drugs."

An interesting thing about this flu protein, though, is that it has only a few mutation variants that affect drug binding but still allow the protein to function. "If we can find the right set of M2 channel blockers, we can stop the progression of the virus," said Dr. Busath. The concept of a cocktail of drugs is not new. In the fight against the HIV AIDS virus, scientists developed a drug cocktail that works well against the virus because it can fight it on multiple fronts. A flu drug in the future might contain a cocktail of drugs to anticipate the virus' mutations.

To discover the right drug or cocktail of drugs, BYU researchers are using new tools for solid state nuclear magnetic resonance spectroscopy developed by Dr. Timothy A. Cross at the National High Magnetic Field Lab at Florida State University to examine the flu M2 protein on the atomic level. Seeing the flu protein at this level allows scientists to experiment with drugs that will plug up the M2 channel and prevent it from reproducing. All influenza type A viruses have the M2 channel as a critical part of their structures. This is encouraging for researchers because once the right drug cocktail is found, it should be effective against all strains of influenza A (H1N1, H3N2, etc.), and it is hoped, against the less common influenza B and C viruses as well.

Dr. Donald Smee, Ph.D., is a research professor at the Institute for Antiviral Research at Utah State University in Logan, Utah. The institute is comprised of a team of scientists, representing a spectrum of disciplines, who work together on research oriented toward the control of viral diseases. Dr. Smee is aware of the research being done at BYU and Florida State as well as other research in the country. "If Dr. Busath's research proves to be effective, it will allow us to be more successful in the testing we perform," said Dr. Smee. "It's looking very promising that in the near future we will have much more effective flu drugs."

The work on influenza M2 at BYU and Florida State University has been funded by a 10-year, multi-million dollar grant from the National Institutes of Health. Dr. Busath and some of his students at BYU are doing the research. Dr. Busath was dragged into flu research "kicking and screaming" by his collaborator, Dr. Cross in 1999. "This is the most exciting research I've done in all my life. It's research that has a very practical application," said Dr. Busath. "This is a blossoming experience and, because of its practical nature, it gets people's attention."

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