Influenza hemagglutinin - sialic acid receptor (HA-SA)

The interaction between influenza hemagglutinin (HA) and sialic acid receptors on host cells is the fundamental first step in the influenza virus infection cycle [12, 13, 19]. Hemagglutinin is a homotrimeric surface glycoprotein that functions as a lectin, specifically recognizing and binding to terminal sialic acid residues on host cell glycoproteins and glycolipids [12, 13, 21]. This binding facilitates the attachment of the virion to the respiratory epithelium and triggers its internalization via receptor-mediated endocytosis [2, 16, 20]. Within the acidic environment of the endosome, HA undergoes an irreversible conformational change that mediates the fusion of the viral envelope with the host membrane, allowing the viral genome to enter the host cytoplasm [2, 13, 19]. As a critical bottleneck for viral entry, this interaction is a major target for therapeutic intervention [4, 8]. Current and experimental drugs include small molecule fusion inhibitors like umifenovir, host-targeted sialidases like DAS181 that enzymatically remove the receptors, and a variety of monoclonal antibodies designed to block either the receptor-binding site or the conserved stalk region [2, 9, 10, 17].

Other names

Hemagglutinin-sialic acid interactionHA-SA complexInfluenza HA receptorSialic acid-containing receptor

Inhibition of viral attachment by blocking the receptor-binding site, inhibition of membrane fusion by binding to the hemagglutinin stalk, enzymatic removal of host sialic acid receptors, and inhibition of hemagglutinin maturation or proteolytic cleavage.