Tuesday, August 26, 2008

Uncovering Influenza's Achilles Heel

 

 

# 2255

 

 

 

One of the `upsides' to our heightened concerns over the H5N1 virus these past 3 years has been that influenza research has received a much needed shot in the arm.    

 

 

Many of these discoveries may someday result in better influenza fighting medicines and technologies, although tangible benefits such as those are likely still years away.  

 

 

Finding an `Achilles heel', a vulnerability across a wide spectrum of influenza viruses - one that can be exploited by a vaccine or an antiviral - has long been the holy grail of influenza researchers.

 

 

New research from the University of Texas at Austin, and Rutgers University, may be bringing us closer to that goal.

 

 

 

This from a press release from the University of Texas.

 

 

 

 

 

Discovery Opens Door for Drugs to Fight Bird Flu, Influenza Epidemics

 

August 25, 2008

 

AUSTIN, Texas — Researchers at The University of Texas at Austin and Rutgers University have reported a discovery that could help scientists develop drugs to fight avian flu and other virulent strains of influenza.

 

The researchers have determined the three-dimensional structure of a site on an influenza A virus protein that binds to one of the human protein targets, thereby suppressing a person's natural defenses to the infection and paving the way for the virus to replicate efficiently. This so-called NS1 virus protein is shared by all influenza A viruses isolated from humans, including avian influenza, or bird flu, and the 1918 pandemic influenza virus.

 

Binding pocket for human CPSF30 protein on influenza A virus NS1 protein

 

This image shows the binding pocket for the human CPSF30 protein on the influenza A virus NS1 protein (brown), with a fragment of the CPSF30 protein (blue) bound in the pocket. Work published this week in the Proceedings of the National Academy of Sciences reveals this interaction is a target for antiviral drug discovery. This image was generated using X-ray crystallography by K. Das, L. Ma, E. Arnold, R. Krug, G. Montelione and others, as part of a collaboration between Rutgers University and The University of Texas at Austin.

 

About 10 years ago, Professor Robert M. Krug at The University of Texas at Austin discovered that the NS1 protein binds a human protein known as CPSF30, which is important for protecting human cells from flu infection. Once bound to NS1, the human protein can no longer generate molecules needed to suppress flu virus replication.

 

Now, researchers led by Krug and Rutgers Professor Gaetano T. Montelione, have identified the specific NS1 binding pocket that grasps the human CPSF30 protein.

 

"Our work uncovers an Achilles heel of influenza A viruses that cause human epidemics and high mortality pandemics," said Montelione, professor of molecular biology and biochemistry at Rutgers. "We have identified the structure of a key target site for drugs that could be developed to effectively combat this disease."

 

A paper detailing the breakthrough discovery appears in the Proceedings of the National Academy of Sciences Early Edition and will be published in an upcoming print issue of the journal.

Krug is also a member of the Institute for Cellular and Molecular Biology at The University of Texas at Austin.

 

(Continue)

 

 

For more information, contact: Lee Clippard, College of Natural Sciences, 512-232-0675; Dr. Robert Krug, 512-232-5563; Dr. Guy Montelione, 732-986-8775.