Peramivir showed strong inhibitory activity against H5N1, H7N1 and H7N7 avian influenza viruses. Anti-viral activity of peramivir was decreased in H5N1 virus containing the H275Y mutation. Peramivir prevented lethality in mice infected with H5N1 virus and also H5N1 virus harboring the H275Y mutation. Peramivir reduced viral titers and levels of proinflammatory cytokines in the lungs of mice infected with H5N1 viruses.