Synthetic sialylphosphatidylethanolamine derivatives bind to human influenza A viruses and inhibit viral infection

We synthesized the sialylphosphatidylethanolamine (sialyl PE) derivatives N eu5Ac-PE, (Neu5Ac)(2)-PE, Neu5Ac-PE (amide) and Neu5Ac-PE (methyl). We exam ined the anti-viral effects of the derivatives on human influenza A virus i nfection by ELISA/virus-binding, hemagglutination inhibition, hemolysis inh ibition and neutralization assays. The sialyl PE derivatives that we examin ed bound to A/Aichi/2/68, A/Singapore/1/57 and A/Memphis/1/71 strains of H3 N2 subtype, but not to A/PR/8/34 strain of H1N1 subtype. The derivatives in hibited viral hemagglutination and hemolysis of human erythrocytes with A/A ichi/2/68 and A/Singapore/1/57 (H3N2), but not with A/PR/8/34 (H1N1). The i nhibitory activity of the (Neu5Ac)(2)-PE derivative was the strongest of al l sialyl PE derivatives (IC50, 35 mu M to 40 mu M). Sialyl PE derivatives a lso inhibited the infection of A/Aichi/2/68 in MDCK cells. Complete inhibit ion was observed at a concentration between 0.3 to 1.3 mM. IC50 of (Neu5Ac) (2)-PE was 15 mu M in A/Aichi/2/68 strain. Taken together, the synthetic si alyl PE derivatives may be effective reagents against infection of some typ es of influenza A viruses.