Influenza virus haemagglutinin, inhibitors

R. Roy, D. Zanini, S. J. Meunier, and A. Romanowska, Solid phase synthesis of dendritic sialoside inhibitors of influenza A virus haemagglutinin, J. Chem. Soc. Chem. Commun. (1993) 1869-1872. 

Roy and coworkers 70 71] described the solid state preparation of the first four generations (e.g., 38) of the dendritic sialoside inhibitors of influenza A virus haemagglutinin... 

Scheme 4.13. Dendritic sialoside inhibitors of influenza A virus haemagglutinin constructed via the solid phase synthesis of a lysine-based superstructure.

The influenza virus is an RNA-(—)- virus and possesses its own RNA polymerase enzyme. The complete RNA genome codes for eight proteins - two structural (matrix) proteins M, and M2, haemagglutinin, and neuraminidase and four proteins involved in replication, three of which make up the polymerase enzyme. Substrates for this are the usual ribonucleosides and there has been some success with the use of nucleoside analogues as inhibitors of the enzyme. The drug ribavirin has been the most successful, although this has to be administered by aerosol. These days, its major use is for the treatment of infections caused by respiratory syncytial viruses (especially in children), since these can cause long-term morbidity. 

Since haemagglutinin is involved in the adhesion of influenza virus to epithelial cells, it is an attractive target for therapeutic intervention. The design and synthesis of potential inhibitors of haemagglutinin has been reviewed elsewhere [5, 7, 14, 17, 33, 34] and, apart from a brief discussion of the general approaches employed towards such anti-influenza agents, is outside the scope of this article. 

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