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Hemagglutinin (HA) is the primary surface glycoprotein of the avian influenza A virus and is essential for viral infectivity (Wikipedia, 2024). It functions as a class I 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 (NIH, 2013). In avian species, HA typically binds to α2,3-linked sialic acids, but mutations can shift specificity to α2,6-linked receptors found in the human respiratory tract, facilitating zoonotic transmission and pandemic potential (MDPI, 2023). As the major antigen on the viral surface, HA is the primary target for neutralizing antibodies and the central component of seasonal and pandemic vaccines (NIH, 2016). Therapeutic strategies targeting HA include small-molecule fusion inhibitors like arbidol and broadly neutralizing antibodies that target the conserved stem region to provide cross-subtype protection (ACS, 2012; NIH, 2021). However, the high rate of antigenic drift and the potential for antigenic shift pose significant challenges, necessitating continuous surveillance and the development of universal vaccine candidates (MDPI, 2023).
Inhibition of viral attachment by blocking the receptor binding site, inhibition of membrane fusion by preventing low-pH induced conformational changes, and inhibition of proteolytic cleavage of the HA0 precursor.
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