Influenza A virus hemagglutinin (HA) and neuraminidase (NA) (HA and NA)

Influenza A virus hemagglutinin (HA) and neuraminidase (NA) are the primary surface glycoproteins of the influenza A virus and serve as the principal targets for both the host immune response and pharmacological interventions [1, 4]. HA is a trimeric protein responsible for viral attachment to host cell sialic acid receptors and subsequent membrane fusion within the endosome, facilitating viral entry [2, 11]. NA is a tetrameric enzyme that cleaves terminal sialic acid residues from host cells and viral glycoproteins, a process essential for the release of newly formed virions and the prevention of viral aggregation [3, 8]. Most seasonal influenza vaccines primarily aim to induce neutralizing antibodies against HA, while the most widely used class of antiviral drugs, neuraminidase inhibitors (e.g., oseltamivir), targets the enzymatic activity of NA [6, 10]. Therapeutic challenges include the rapid evolution of these proteins through antigenic drift and shift, which necessitates annual vaccine updates and leads to the emergence of drug-resistant viral strains [13, 14].

Other names

Influenza surface glycoproteinsH and N antigensHemagglutinin-neuraminidaseHA/NA

Neuraminidase inhibitors (NAIs) competitively bind to the active site of the neuraminidase enzyme, preventing the cleavage of sialic acid residues and thereby trapping progeny virions on the host cell surface to limit viral spread [1, 6]. Hemagglutinin-targeted agents, including neutralizing antibodies and small-molecule fusion inhibitors like umifenovir, act by blocking the initial attachment of the virus to sialic acid receptors or by stabilizing the HA trimer to prevent the low-pH-induced conformational change required for membrane fusion and viral genome release [2, 11].