Inhibition of viral adhesion and XXXX by @entity3167 -conjugated dendritic polymers.

@entity1 @entity3167 @entity683 @entity281 @entity2343 @entity2975 @entity33105
Multiple @entity3167 (SA) residues conjugated to a linear @entity2975 backbone are more effective than monomeric SA at inhibiting @entity683 -induced agglutination of red blood cells. However, "polymeric inhibitors" based on @entity2975 backbones are cytotoxic. @entity2343 offer a nontoxic alternative to @entity2975 and may provide a variety of potential synthetic inhibitors of @entity683 virus adhesion due to the wide range of available polymer structures. We evaluated several dendritic polymeric inhibitors, including spheroidal, linear, linear-dendron copolymers, comb-branched, and dendrigraft polymers, for the ability to inhibit virus hemagglutination (HA) and to block @entity281 of @entity1 cells in vitro. Four viruses were tested: @entity683 A @entity33105 (selectively propagated two ways), X-31 @entity683 A H3N2, and sendai. The most potent of the linear and spheroidal inhibitors were 32-256-fold more effective than monomeric SA at inhibiting HA by the @entity33105 @entity683 virus. Linear-dendron copolymers were 1025-8200-fold more effective against @entity33105 @entity683 , X-31 @entity683 , and sendai viruses. The most effective were the comb-branched and dendrigraft inhibitors, which showed up to 50000-fold increased activity against these viruses. We were able to demonstrate significant (p < 0.001) dose-dependent reduction of @entity683 @entity281 in @entity1 cells by polymeric inhibitors, the first such demonstration for multivalent SA inhibitors. Effective dendrimer polymers were not cytotoxic to @entity1 cells at therapeutic levels. Of additional interest, variation in the inhibitory effect was observed with different viruses, suggesting possible differences due to specific growth conditions of virus. SA-conjugated dendritic polymers may provide a new therapeutic modality for viruses that employ SA as their target receptor.
