Synthetic sialylphosphatidylethanolamine derivatives bind to human influenza A viruses and inhibit viral infection.
We synthesized the sialylphosphatidylethanolamine (sialyl PE) derivatives Neu5Ac-PE, (Neu5Ac)2-PE, Neu5Ac-PE (amide) and Neu5Ac-PE (methyl). We examined the anti-viral effects of the derivatives on human influenza A virus infection by ELISA/virus-binding, hemagglutination inhibition, hemolysis inhibition and neutralization assays. The sialyl PE derivatives that we examined bound to A/Aichi/2/68, A/Singapore/1/57 and A/Memphis/1/71 strains of H3N2 subtype, but not to A/PR/8/34 strain of H1N1 subtype. The derivatives inhibited viral hemagglutination and hemolysis of human erythrocytes with A/Aichi/2/68 and A/Singapore/1/57 (H3N2), but not with A/PR/8/34 (H1N1). The inhibitory activity of the (Neu5Ac)2-PE derivative was the strongest of all sialyl PE derivatives (IC50, 35 microM to 40 microM). Sialyl PE derivatives also inhibited the infection of A/Aichi/2/68 in MDCK cells. Complete inhibition was observed at a concentration between 0.3 to 1.3 mM. IC50 of (Neu5Ac)2-PE was 15 microM in A/Aichi/2/68 strain. Taken together, the synthetic sialyl PE derivatives may be effective reagents against infection of some types of influenza A viruses.
Guo
C T
CT
Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, Japan.
Wong
C H
CH
Kajimoto
T
T
Miura
T
T
Ida
Y
Y
Juneja
L R
LR
Kim
M J
MJ
Masuda
H
H
Suzuki
T
T
Suzuki
Y
Y
D000914:Antibodies, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D006386:Hemagglutination Tests; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D009980:Influenza A virus / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D000914:Antibodies, Viral; D000998:Antiviral Agents; D010714:Phosphatidylethanolamines