Influenza hemagglutinin-sialic acid interface (HA-SA interface)

The influenza virus surface glycoproteins, primarily hemagglutinin (HA), facilitate the initial step of viral infection by recognizing and binding to sialic acid receptors on the host cell membrane (Skehel & Wiley, 2000). This attachment interface is a major determinant of viral tropism and host specificity, with human-adapted viruses typically preferring alpha 2,6-linked sialic acids found in the upper respiratory tract, whereas avian strains prefer alpha 2,3-linked receptors (UniProt P03435). Therapeutic intervention at this interface aims to prevent viral entry, involving the use of neutralizing monoclonal antibodies that bind to the HA head or stem, small molecules like umifenovir that stabilize the HA structure to prevent fusion, and host-directed enzymes like DAS181 that enzymatically remove the sialic acid receptors (Malakhov et al., 2006; Kadam & Wilson, 2017). Because the HA protein is the primary target of the host immune response, it undergoes frequent mutations known as antigenic drift, which presents a significant challenge for maintaining the long-term efficacy of drugs and vaccines targeting this interface (Chen et al., 2020).

Other names

HA-SA interfaceInfluenza attachment siteHemagglutinin-receptor binding siteSialic acid binding pocketInfluenza entry interface

Inhibition of viral attachment to host cell receptors and prevention of subsequent hemagglutinin-mediated membrane fusion.