click to enlarge   Image generated using X-ray crystallography shows 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. This interaction is a target for antiviral drug discovery. (Source: K. Das, L. Ma, E. Arnold, R, Krug, G. Montelione and others, Rutgers University and The University of Texas at Austin)

Researchers at Rutgers University and The University of Texas at Austin have reported a discovery that could help scientists develop drugs to fight the much-feared bird 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 its 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. A paper detailing this breakthrough discovery appears in the Proceedings of the National Academy of Sciences Early Edition and will be published in an upcoming issue of the print edition.

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 Rutgers Professor Gaetano T. Montelione and Krug identified the novel 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. “We have identified the structure of a key target site for drugs that could be developed to effectively combat this disease.”

Release date: august 25, 2008
Source: Rutgers, The State University of New Jersey