Prevention of influenza pneumonitis by sialic Acid-conjugated dendritic polymers.
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 32-170 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.
Landers
Jeffrey J
JJ
Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, University of Michigan, Ann Arbor, Michigan 48109, USA. landersj@med.umich.edu
Cao
Zhengyi
Z
Lee
Inhan
I
Piehler
Lars T
LT
Myc
Piotr P
PP
Myc
Andrzej
A
Hamouda
Tarek
T
Galecki
Andrzej T
AT
Baker
James R
JR
D000818:Animals; D002240:Carbohydrate Sequence; D015195:Drug Design; D006384:Hemagglutination; D006801:Humans; D009980:Influenza A virus / Q000145:classification / Q000472:pathogenicity*; D007251:Influenza, Human / Q000150:complications*; D008168:Lung / Q000187:drug effects / Q000821:virology; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011014:Pneumonia / Q000517:prevention & control* / Q000821:virology*; D011073:Polyamines; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D012794:Sialic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*
D011073:Polyamines; D011108:Polymers; D012794:Sialic Acids