The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase possessing endonuclease activity, wherein the PA subunit is from Influenza A 2009 pandemic H1N1 virus or is a variant thereof. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of the polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of the polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods of identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit the endonucleolytic activity, as well as the compounds themselves. Preferably, the compounds are identifiable by the methods disclosed herein or the pharmaceutical compositions are producible by the methods disclosed herein.
