Prevention of Influenza Pneumonitis by Sialic Acid-Conjugated Dendritic Polymers
Journal Article - Open Access
MICHIGAN UNIV ANN ARBOR ANN ARBOR United States
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Influenza A viral infection begins by hemagglutinin glycoproteins on the viral envelope binding to cell membrane sialic acid SA. Free SA monomers cannot block hemagglutinin adhesion in vivo because of toxicity. Polyvalent, generation 4 G4 SA-conjugated polyamidoamine PAMAM dendrimer G4-SA was evaluated as a means of preventing adhesion of 3 influenza A subtypes H1N1, H2N2, and H3N2. In hemagglutination-inhibition assays, G4-SA was found to inhibit all H3N2 and 3 of 5 H1N1 influenza subtype strains at concentrations 32170 times lower than those of SA monomers. In contrast, G4-SA had no ability to inhibit hemagglutination with H2N2 subtypes or 2 of 5 H1N1 subtype strains. In vivo experiments showed that G4-SA completely prevented infection by a H3N2 subtype in a murine influenza pneumonitis model but was not effective in preventing pneumonitis caused by an H2N2 subtype. Polyvalent binding inhibitors have potential as antiviral therapeutics, but issues related to strain specificity must be resolved.
- Medicine and Medical Research