Influenza virus hemagglutinin and neuraminidase surface proteins (HA/NA)

Influenza virus hemagglutinin (HA) and neuraminidase (NA) are the two primary surface glycoproteins of the influenza virus, essential for its infectivity and spread [1, 6]. HA is a class I fusion protein that mediates viral entry by binding to sialic acid receptors on the host cell surface and facilitating the fusion of the viral envelope with the endosomal membrane [4, 12]. NA is an exo-alpha-sialidase enzyme that cleaves terminal sialic acid residues from host cell surfaces and progeny virions, preventing viral aggregation and enabling the release of new virus particles [9, 15]. These proteins are the main targets of the host immune system and are the key components of seasonal and pandemic influenza vaccines [8, 20]. Pharmacological intervention primarily targets NA with inhibitors like oseltamivir to limit viral spread, while HA is a target for entry inhibitors like umifenovir and broadly neutralizing antibodies [2, 10, 14]. The high rate of mutation in these proteins, known as antigenic drift and shift, necessitates frequent vaccine updates and poses a constant challenge for drug efficacy due to the emergence of resistant strains [13, 22].

Other names

Influenza surface glycoproteinsHA and NAInfluenza envelope proteinsInfluenza surface antigens

Neuraminidase inhibitors (e.g., oseltamivir) block the enzymatic activity of NA, preventing the cleavage of sialic acid and thus inhibiting the release of progeny virions from infected cells [7, 10]. Hemagglutinin inhibitors (e.g., umifenovir) target the HA protein to block viral entry by either preventing attachment to host sialic acid receptors or inhibiting the pH-dependent conformational change required for membrane fusion [2, 14].