The present invention relates to soluble fragments of the Influenza virus RNAdependent RNA polymerase subunit PB2 and variants thereof, and crystallizedcomplexes thereof comprising an RNA cap analog. This invention also relatesto computational methods using the structural coordinates of said complex toscreen for and design compounds that interact with the RNA cap binding pocket.In addition, this invention relates to methods identifying compounds that bindto PB2 polypeptide fragments comprising the RNA cap binding pocket, preferablyinhibit the interaction with RNA caps or analogs thereof, by using said PB2 polypeptidefragments, preferably in a high-throughput setting. This invention also relatesto compounds and pharmaceutical compositions comprising the identified compoundsfor the treatment of disease conditions due to viral infections caused by negative-sensesingle stranded RNA viruses.
