Influenza virus hemagglutinin and SARS-CoV-2 spike protein (HA/S)

Influenza virus hemagglutinin (HA) and SARS-CoV-2 spike (S) protein are the primary surface glycoproteins responsible for viral entry into host cells (UniProt P03435; UniProt P0DTC2). Both function as Class I fusion proteins that mediate binding to specific host receptors—sialic acids for HA and ACE2 for the S protein—followed by the fusion of viral and cellular membranes (PubMed: 32155444). As the principal antigens exposed on the virion surface, they are the primary targets for neutralizing antibodies induced by infection or vaccination (PubMed: 27117404). Therapeutic interventions include monoclonal antibodies like Sotrovimab or MedI8852 that block receptor binding or fusion, as well as vaccines designed to elicit a robust immune response against these proteins (NIH COVID-19 Guidelines). However, both targets are subject to significant evolutionary pressure, leading to mutations that can result in immune escape and reduced efficacy of existing medical countermeasures (Nature Reviews Microbiology, 2021). These proteins are considered indirect immunological targets because they are targeted by the immune system's components (antibodies) rather than being the direct site of action for most traditional small-molecule drugs.

Other names

HemagglutininHASpike proteinS proteinSpike glycoproteinSurface glycoproteinViral fusion protein

Neutralization of viral entry by blocking receptor binding (sialic acid or ACE2) or inhibiting the conformational change required for membrane fusion.