Sialidase rational drug design

Dyason JC, Wilson JC, Von Itzstein M. Sialidases Targets for rational drug design. In Bultinck P, De Winter H, Langenaeker W, Tollenaere JP, editors. Computational medicinal chemistry for drug discovery. New York Dekker, 2004. 

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]. 

The most studied sialidase is the influenza virus neuraminidase, whose structure was reported over 15 years ago [9], and which has been the target of highly successful rational drug design [10-12]. Influenza type A and B viruses have two surface proteins, hemagglutinin (HA) which attaches the virus to host cells by recognizing sialic... 

Drug Discovery, P. Bultinck, H. De Winter, W. Langenaeker, and J. P. Tollenaere, Eds., Dekker, New York, 2004. Sialidases Targets for Rational Drug Design. 

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