Polymeric inhibitor of influenza virus attachment protects mice from experimental influenza infection.
Synthetic sialic acid-containing macromolecules inhibit influenza virus attachment to target cells and suppress the virus-mediated hemagglutination and neutralize virus infectivity in cell culture. To test the protective effects of attachment inhibitors in vivo, mice were infected with mouse-adapted influenza virus A/Aichi/2/68 (H3N2) and treated with synthetic polyacrylamide-based sialylglycopolymer PAA-YDS bearing moieties of (Neu5Acalpha2-6Galbeta1-4GlcNAcbeta1-2Manalpha1)2-3,6Manbeta1-4GlcNAcbeta1-4GlcNAc. Single intranasal inoculations with PAA-YDS 30 min before or 10 min after infection increased the survival of mice (P<0.01). Multiple treatments with aerosolized PAA-YDS on days 2-5 post infection also increased survival (P<0.01), alleviated disease symptoms, and decreased lesions in the mouse lungs. These data suggest that synthetic polyvalent inhibitors of virus attachment can be used for prevention and treatment of influenza.
Gambaryan
A S
AS
M.P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, 142 782, Moscow, Russia.
Tuzikov
A B
AB
Chinarev
A A
AA
Juneja
L R
LR
Bovin
N V
NV
Matrosovich
M N
MN
D000180:Acrylic Resins / Q000737:chemistry / Q000627:therapeutic use; D000280:Administration, Inhalation; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D002240:Carbohydrate Sequence; D004195:Disease Models, Animal; D015195:Drug Design; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000627:therapeutic use*; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000502:physiology; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000473:pathology; D014779:Virus Replication; D000099166:Polyacrylamides
D000180:Acrylic Resins; D000998:Antiviral Agents; D009844:Oligosaccharides; D000099166:Polyacrylamides; C016735:sialooligosaccharides