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Influenza A viruses contain sialic acid (SIA) receptor‐binding hemagglutinin (HA) and receptor‐destroying neuraminidase (NA). The balance between HA and NA is adjusted to the SIA receptor repertoire of the host species. Besides a conserved catalytic site, NA carries a 2nd SIA‐binding site (2SBS). The 2SBS enhances the activity of the catalytic site and affects the HA‐NA balance. Conservation or loss of the 2SBS is associated with (changes in) host tropism.

Second sialic acid‐binding site of influenza A virus neuraminidase: binding receptors for efficient release