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 said PA subunit is from Influenza A 2009 pandemic HlNl virus or is a variant thereof. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said 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 identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting. This invention also relates to compounds which are able to modulate, preferably to inhibit, the endonuclease activity of the PA subunit polypeptide fragment or variant thereof of the present invention and pharmaceutical compositions comprising said compounds for the treatment of disease conditions caused by viral infections with viruses of the Orthomyxoviridae family, Bunyaviridae family and/or Arenviridae family, preferably caused by viral infections with Influenza A 2009 pandemic HlNl virus. Preferably, said compounds are identifiable by the methods disclosed herein or said pharmaceutical compositions are producible by the methods disclosed herein.La présente invention concerne des fragments polypeptidiques comprenant un fragment amino-terminal de la sous-unité PA dune ARN polymérase ARN-dépendante virale possédant une activité endonucléasique, ladite sous-unité PA provenant du virus H1N1 pandémique de la grippe A de 2009 ou étant un de ses variants. Cette invention concerne également (i) des cristaux des fragments polypeptidiques qui conviennent à la déterminatio
