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Hemagglutinin (HA) is the primary surface glycoprotein of the Influenza A virus H3N2 variant (H3N2v), a zoonotic strain that circulates in swine and occasionally infects humans (CDC, 2021). It plays a critical role in the viral life cycle by mediating the binding of the virus to sialic acid receptors on the surface of host respiratory cells and facilitating the fusion of the viral envelope with the host cell membrane within endosomes (UniProt, 2023). The H3N2v strain is characterized by the inclusion of the M gene from the 2009 H1N1 pandemic virus, which may influence its stability and transmission (CDC, 2021). As the major antigen on the viral surface, HA is the principal target for neutralizing antibodies induced by vaccination or natural infection. Therapeutic interventions targeting HA include seasonal vaccines, candidate pandemic vaccines, and experimental monoclonal antibodies designed to provide broad protection by targeting the conserved stem region of the protein (Nature Communications, 2018). However, the rapid evolution of the HA protein through antigenic drift remains a significant challenge for long-term vaccine efficacy and drug development (Nature Reviews Microbiology, 2018).
Inhibition of viral attachment to host cell sialic acid receptors and prevention of pH-dependent membrane fusion (UniProt, 2023; PubChem, 2023).
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