New Targets to Fight Flu

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Influenza A is a major human and animal pathogen with the ability to mutate and cross species: the recent emergence of the H5N1 strain of the Avian Influenza A virus has emphasised the need for new treatments. Between 2003 and 2008 there were 385 confirmed human cases of the avian H5N1 strain (WHO data).
Existing flu treatments such as Tamiflu® and Relenza® target the viral neuraminidase, a highly variable protein on the surface of the virus which can mutate to give viral strains which are resistant to the drugs.
PA-PB1 Complex (pdb id: 3cm8)

PA-PB1 Complex (pdb id: 3cm8)

Two independent reports (He et.al., Obayashi et.al.) have recently described the crystal structure of the viral RNA polymerase, a protein complex that is essential for viral transcription and replication. The complex contains three proteins, PB1 which has polymerase and endonuclease activities, PB2 which is responsible for binding capped RNA, and PA, the function of which is less clear. Both structures show large fragments of PA bound to a smaller helical fragment of PB1. If it were possible to devise a small molecule that could disrupt this binding, it would likely prevent polymerase activity and viral replication. Although protein-protein interactions are considered to be difficult targets for drug discovery, in this case the binding area is relatively small and offers a potential target for novel anti-influenza drugs.


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