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Influenza A virus hemagglutinin H3 is a major surface glycoprotein of the influenza A virus, specifically the H3 subtype, which is a primary cause of seasonal epidemics in humans (UniProt P03437). It functions as a class I viral fusion protein, mediating both the initial attachment of the virus to host cell sialic acid receptors and the subsequent fusion of the viral envelope with the endosomal membrane (PubMed: 22226355). This fusion process is triggered by a low-pH-induced conformational change within the endosome, allowing the viral genome to enter the host cytoplasm (NCBI: NBK11440). H3 is the principal antigen targeted by seasonal influenza vaccines, which induce antibodies that typically block the receptor-binding site on the HA head (CDC: Influenza (Flu) Viruses). However, the virus frequently undergoes antigenic drift, leading to mutations that allow it to evade existing immunity and necessitating annual vaccine updates. Therapeutic interventions targeting H3 include the fusion inhibitor Umifenovir and various monoclonal antibodies in development that target the more conserved stem region to provide broader protection (DrugBank: DB13609; PubMed: 30104376).
Inhibition of viral attachment to host cells and prevention of pH-dependent membrane fusion.
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