Hemagglutinin protein of Influenza virus (HA)

Hemagglutinin protein (HA) is a homotrimeric transmembrane glycoprotein expressed on the surface of Influenza A and B virions, comprising HA1 (responsible for receptor binding) and HA2 (responsible for membrane fusion). It is essential for initiating infection: HA binds to sialic acid residues on host cells and facilitates viral fusion after endocytosis in a low pH endosome. The precursor (HA0) is cleaved by host proteases to yield functional HA1 and HA2 regions, joined by disulfide bonds and other stabilizing interactions. HA is the principal antigenic determinant, eliciting protective immune responses and serving as the primary target for neutralizing antibodies, vaccines, and therapeutic monoclonals. Antigenic variation (drift and shift) in HA underlies seasonal flu epidemics and pandemic potential; HAs are classified into multiple subtypes (H1–H16 for Influenza A) with distinct group-specific properties. Hemagglutinin is routinely used in hemagglutination assays for diagnosis and efficacy monitoring. Therapeutically, the high variability of HA poses substantial challenges, but conserved regions offer opportunities for broad-spectrum immunomodulation.

Other names

Influenza hemagglutininHAInfluenza virus hemagglutininHaemagglutinin (British English)

Drugs targeting Hemagglutinin protein act by inhibiting receptor binding (e.g., antibodies blocking the HA head domain), inhibiting membrane fusion (e.g., antibodies or inhibitors targeting the HA stem domain, preventing pH-triggered conformational changes), or preventing hemagglutination (serological blockade). Baloxavir marboxil and Favipiravir have less direct mechanisms but can indirectly affect HA cleavage or viral replication.