The interaction between viral HA (hemagglutinin) and oligosaccharide of the host plays an important role in the infection and transmission of avian and human flu viruses. Until now, this interaction has been classified by sialyl(${alpha}2-3$) or sialyl(${alpha}2-6$) linkage specificity of oligosaccharide moieties for avian or human virus, respectively. In the case of H5N1 and newly mutated flu viruses, classification based on the linkage type does not correlate with human infection and human-to-human transmission of these viruses. It is newly suggested that flu infection and transmission to humans require high affinity binding to the extended conformation with long length sialyl(${alpha}2-6$)galactose containing oligosaccharides. On the other hand, the avian flu virus requires folded conformation with sialyl(${alpha}2-3$) or short length sialyl(${alpha}2-6$) containing trisaccharides. This suggests a potential future direction for the development of new species-specific antiviral drugs to prevent and treat pandemic flu.