Suppression of influenza virus infection by an N-thioacetylneuraminic acid acrylamide copolymer resistant to neuraminidase.
We have previously shown that alpha-2-O-methyl-5-N-thioacetylneuraminic acid (alpha-Neu5thioAc2Me) has a higher affinity to bromelain-treated hemagglutinin (HA) of influenza A virus than sialic acid from natural sources (Machytka et al., 1993, FEBS Lett. 334, 117-120). We have now compared the inhibitory effects of alpha-Neu5thioAc2Me and other sialic acid analogs on receptor binding and plaque formation of intact influenza A viruses. When alpha-Neu5thioAc2Me was polymerized by conjugation to polyacrylamide, its affinity to HA increased 10(3)-fold. When analyzed by plaque reduction, the alpha-Neu5thioAc2 polymer was about 10 times more efficient as an inhibitor of virus replication than the alpha-Neu5Ac2 polymer, stressing the importance of sulfur at C5. The S-glycoside alpha-2-S-methyl-5-N-thioacetylneuraminic acid (alpha-Neu5thioAc2SMe) 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 alpha-Neu5thioAc2S polymer has the potential to be used as an inhibitor of influenza virus infection.
Itoh
M
M
Institut für Virologie, Philipps-Universität Marburg, Germany.
Hetterich
P
P
Isecke
R
R
Brossmer
R
R
Klenk
H D
HD
D000180:Acrylic Resins; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D002645:Chickens; D006027:Glycosides / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009438:Neuraminic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009439:Neuraminidase / Q000378:metabolism; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011991:Receptors, Virus / Q000378:metabolism; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects; D000509:alpha-Fetoproteins / Q000378:metabolism; D000099166:Polyacrylamides
D000180:Acrylic Resins; D000998:Antiviral Agents; D006027:Glycosides; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D009438:Neuraminic Acids; D009439:Neuraminidase; D011108:Polymers; D011991:Receptors, Virus; D000509:alpha-Fetoproteins; D000099166:Polyacrylamides