POLYPEPTIDE FRAGMENTS OF PANDEMIC INFLUENZA VIRUS A 2009 H1N1 HAVING ENDONUCLEASE ACTIVITY, AND THEIR USE

摘要

PROBLEM TO BE SOLVED: To provide pharmacological compositions for treating infectious diseases, the composition being able to modulate the endonuclease activity of the viral polymerase of Influenza A 2009 pandemic H1N1 virus.SOLUTION: A polypeptide fragment comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase possessing endonuclease activity relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of above polypeptide fragments using X-ray crystallography, and to (ii) computational methods using the structural coordinates of the polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytic active site within the polypeptide fragment. The invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit above endonucleolytic activity, preferably in a high throughput setting.SELECTED DRAWING: None