SUPPRESSION OF INFLUENZA-VIRUS INFECTION BY AN N-THIOACETYLNEURAMINICACID ACRYLAMIDE COPOLYMER RESISTANT TO NEURAMINIDASE

We have previously shown that alpha-2-O-methyl-5-N-thioacetylneuramini c acid (alpha-Neu5thioAc2Me) has a higher affinity to bromelain-treate d hemagglutinin (HA) of influenza A virus than sialic acid from natura l sources (Machytka at al., 1993, FEES Lett 334, 117-120). We have now compared the inhibitory effects of alpha-Neu5thioAc2Me and other sial ic acid analogs on receptor binding and plaque formation of intact inf luenza A viruses. When alpha-Neu5thioAc2Me was polymerized by conjugat ion to polyacrylamide, its affinity to HA increased 10(3)-fold. When a nalyzed by plaque reduction, the alpha-Neu5thioAc2 polymer was about 1 0 times more efficient as an inhibitor of virus replication than the a lpha-Neu5Ac2 polymer, stressing the importance of sulfur at C5. The S- glycoside alpha-2-S-methyl-5-N-thioacetylneuraminic acid (alpha-Neu5th ioAc2SMe) had the same affinity to HA as alpha-Neu5thioAc2Me, but was resistant to neuraminidase. The alpha-Neu5thioAc2S polymer interfered with the replication of a wider spectrum of influenza A virus subtypes than the alpha-Neu5thioAc2 polymer. The results indicate that the alp ha-Neu5thioAc2S polymer has the potential to be used as an inhibitor o f influenza virus infection. (C) 1995 Academic Press, Inc.