Influenza virus sialidase, catalytic site

Another important feature, especially from the viewpoint of rational drug design, zanamivir (12) shows a remarkable degree of selectivity towards influenza virus sialidase. In experiments aimed at determining the specificity of (12) towards influenza sialidase it was shown that zanamivir [as well as the 4-amino derivative (11)] did not show any increase in inhibition of other viral, bacterial, or mammalian sialidases when compared with Neu5Ac2en (6) [73, 87]. The results of some of these studies are presented in the clinical summary section of this article. This selectivity has been explained on the basis of the active site architecture of the different sialidases, in that it is only influenza virus sialidase which can accomodate the relatively bulky and basic C-4 substituent in its catalytic site [73]. 

Figure 2. The structure of the sialidase of influenza A virus. The model has been derived from the crystallographic data obtained on A/tem/Australia/G70C/75 sialadase (Baker et al., 1987). View of the monomer is down the fourfold symmetry axis. The catalytic site (white) is indicated. The receptor binding site (black) observed on some sialidase molecules is also shown. For details see text.

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