SYNTHETIC STRATEGIES FOR ANTI-VIRAL DRUG DESIGN

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This research will develop compounds that interfere with attachment of influenza virus to cells (and detachment from cells). Its objectives are: . To develop synthetic routes to analogs of sialic acids and structurally related compounds, and to use these compounds to block the sialic acid binding sites of viral hemagglutinin (HA) and of neuraminidase (NA). . To prepare bi, tri-, and multivalent versions of these compounds, to take advantage of cooperative polyvalent interaction between them and HA and NA on the surface of the virus. . To prepare polymeric, polyvalent compounds by free-radical polymerization of appropriately functionalized monomers containing analogs of sialic acids, and to evaluate the importance of "steric inhibition" of binding of virus to cell using these polymers. . To develop and implement new types of assays relevant to these interactions, including assays based on embryonated chicken eggs and on affinity capillary electrophoresis. . To begin to extend the general principles established in studying influenza virus to other viruses and to bacterial pathogens.