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Possible adaptation of one of the currently circulating strains of highly pathogenic H5N1 avian influenza A virus to produce the next human influenza pandemic is an area of major global concern. Intense research is being focused on developing new generations of effective vaccines and antivirals. Here, we discuss the structure of hemagglutinin and its potential as a target for development of future therapeutics to mitigate the impact of any future influenza pandemic.