Analogue inhibitors by modifying oseltamivir based on the crystal neuraminidase structure for treating drug-resistant H5N1 virus.

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Du QS, Wang SQ, Chou KC

Analogue inhibitors by modifying oseltamivir based on the crystal neuraminidase structure for treating drug-resistant H5N1 virus.

Biochem Biophys Res Commun. 2007 Oct 19;362(2):525-31. Epub 2007 Aug 13.

PubMed ID

17707775 [ View in PubMed

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Abstract

The worldwide spread of H5N1 avian influenza and the increasing reports about its resistance to the existing drugs have made a priority for the development of the new anti-influenza molecules. The crystal structure of H5N1 avian influenza neuraminidase reported recently by Russell et al. [R.J. Russell, L.F. Haire, D.J. Stevens, P.J. Collins, Y. P. Lin, G.M. Blackburn, A.J. Hay, S.J. Gamblin, J.J. Skehel, The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design, Nature 443 (2006) 45-49] have provided new opportunities for drug design in this regard. It is revealed through the structure that the active sites of the group-1 neuraminidases, which contain the N1 subtype, have a very different three-dimensional structure from those of group-2 neuraminidases. The key difference is in the 150-loop cavity adjacent to the conserved active site in neuraminidase. Based on these findings and by modifying oseltamivir, six analog inhibitors were proposed as candidates for developing inhibitors against H5N1 virus, particularly against the oseltamivir-resistant H5N1 virus strain.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Oseltamivir	Neuraminidase	Protein	Influenza A virus (strain A/Chile/1/1983 H1N1)	Yes	Inhibitor	Details