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H5N1 bird flu has seemed a likely pandemic threat for decades, but the first new influenza virus to emerge as an imminent pandemic threat in the 21^st century is H1N1 swine flu. The drug oseltamivir (Tamiflu®) inhibits flu neuraminidase, a component necessary for virus spread, in susceptible flu strains. Luckily H1N1 swine flu is susceptible (at least in early May, 2009). The development of oseltamivir was guided, in part, by crystallographically determined structures of flu neuraminidase. Neuraminidase is a homotetramer, shown with oseltamivir bound (). Here is . Oseltamivir was designed to fit N2/N9 (neuraminidases from other strains of flu). Serendipitously, it also fits N1, doing so by (induced fit). The most common mutation in N1 that confers resistance to oseltamivir is H274Y. The mutant tyrosine prevents oseltamivir from fitting, but still allows . (more...)