Researchers identify ultimate drug targets against flu viruses
Berlin – German researchers have laid the groundwork for the development of long-lasting flu drugs that could sidestep the viruses’ genetic variability. The researchers, headed by Thomas Meyer from the Max Planck Institute for Infection Biology, did not screen for drug targets in the virus but instead conducted screening in their human hosts. This was achieved by knocking down individual genes in human lung cell cultures ba RNA interference (RNAi) before infecting them with the flu virus (Nature, doi:10.1038/nature08760). The results of the systematic RNAi screen suggest that some targets may have broad-spectrum therapeutic potential against multiple influenza strains, with a minimal risk for the viruses becoming resistant against the drugs that target host genes essential for viral infection. Meyer’s team, who opened their BSL 3 lab just two months ago (more....), identified 168 genes (59% of all 287 candidate genes screened) inhibiting either the endemic H1N1 (119 genes) or the current pandemic H1N1 influenza A virus strains (121). A subset of common genes was also deemed essential for the replication of a highly pathogenic avian H5N1 bird flu strain. Inhibition of one of the targets, the cdc kinase, with a small molecule inhibitor reduced influenza virus replication by more than two orders of magnitude. Other targets significantly reduced flu infection symptoms in an animal model. The study also highlights the validity of targeting the host rather than viral factors – existing drugs directed against viral targets all too often lose efficacy as the virus mutates and builds up resistance.