POLYACRYLAMIDES BEARING PENDANT ALPHA-SIALOSIDE GROUPS STRONGLY INHIBIT AGGLUTINATION OF ERYTHROCYTES BY INFLUENZA-VIRUS - THE STRONG INHIBITION REFLECTS ENHANCED BINDING THROUGH COOPERATIVE POLYVALENT INTERACTIONS

An ELISA assay is described for measuring the binding of influenza vir us A-X31 to alpha-sialoside groups that are linked to biotin-labeled p olyacrylamides. The efficacy of these polymers in inhibiting the adhes ion of influenza virus to erythrocytes (as measured by a hemagglutinat ion assay) was shown to be directly related to the binding affinity of the polymers for the viral surface: the differences in inhibitory eff icacy among the polymeric inhibitors and monomeric alpha-methyl sialos ide, among fractions of a polymeric, polyvalent inhibitor with narrow molecular weight ranges, and among polymeric inhibitors prepared by co polymerization or modification of a preformed polymer chain, all corre lated with differences in the affinity of the inhibitors for the surfa ce of the virus, The polymeric inhibitors studied had affinities for t he viral surface that ranged between 10(3) and > 10(6) greater than al pha-methyl sialoside, on the basis of total sialic acid groups in solu tion, The role of steric stabilization in the mechanism by which these polymers inhibit hemagglutination was investigated, The ability of th e polymeric, polyvalent inhibitors to inhibit the binding of a polyclo nal antibody to the viral surface suggests that steric stabilization m ay also be an important effect in this system.