Grenoble scientists discover the deadly “knife” of influenza



flu virusmic.jpgDisarming the flu virus has become a key strategy in the battle against the flu. Scientists in Grenoble in France have made a breakthrough in research into how the virus attacks the human body.  Powerful X-ray imaging has enabled them to learn more about its main weapon  - a so called "knife"  used by the virus to access and hijack human proteins  which it needs to reproduce. Deprive the virus of its knife and the battle is won so the theory goes.

To replicate itself, the influenza virus on accessing the cells takes control of several key processes and exactly how this is done is a long-standing subject of scientific enquiry. In this week's Nature, a high-resolution image of a part of the virus shows how the virus hijacks the cell's RNA molecules for its own purposes, opening a new approach to drugs which inhibit this action.

Scientists have now discovered which part of the virus does the cutting. The part of the virus which contained the knife used for this operation has been a big puzzle for a long time. Until now it was generally thought that this knife had a very complicated structure. But researchers have found it's relatively simple and easy to reproduce.
The group of researchers from Grenoble used the powerful X-ray beams of the European Synchrotron Radiation Facility (ESRF) to produce three-dimensional images of a "knife" which plays a crucial role in this piracy.

Stephen Cusack, Scientist at Grenoble outstation of EMBL: " I think this discovery is going to help us alot in the design of anti influenza drugs. Now we know exactly where the knife in the virus is, we can use high-resolution structure to design chemicals that specifically inhibit this activity. Indeed there has been some work that has obviously been done in the past on this but now the new information will allow us to build on this and improve it and come up with drugs that will stop infections of influenza in cells".

For their discovery, the researchers produced hundreds of crystals which all needed scanning at the ESRF to find the handful suitable for analysis. Rapid access to X-ray beam time and development of automated measurement facilities allowed them to perfect crystals of the necessary quality in a comparatively short time. Such efforts matter, as new drugs and vaccines against influenza are desperately sought. Seasonal epidemics kill several hundreds of thousands of people across the world every year, and a global pandemic looms if bird flu strains develop the ability to infect humans easily. Some scientists believe that this grim prospect is just a matter of time.

Important as the breakthrough in Grenoble is, the researchers involved caution that the development of the right kind of drugs could take ten years. But with flu remaining such a threat, it's nothing to be sneezed at.

High resolution image of the key domain of the influenza virus polymerase. Credit: Stephen Cusack/EMBL.

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