Influenza A virus hemagglutinin H3 subtype receptor-binding site (H3 HA RBS) (H3 HA RBS)

The Influenza A virus hemagglutinin H3 subtype receptor-binding site (RBS) is a shallow pocket located on the distal globular head of the hemagglutinin (HA) glycoprotein [1.1.1, 1.1.4]. Its primary biological function is to facilitate viral attachment by binding to sialic acid-containing receptors on the host cell surface, with human-adapted H3 strains showing a preference for alpha-2,6-linked sialic acids [1.2.2, 1.2.3]. The RBS is composed of highly conserved residues at its base (e.g., Tyr98, Trp153, His183) and more variable structural elements including the 130-loop, 150-loop, 190-helix, and 220-loop [1.1.1, 1.2.1]. Because it is a primary target for neutralizing antibodies, the RBS and its surrounding loops are subject to intense selective pressure, leading to frequent antigenic drift and the emergence of escape mutants [1.2.3, 1.3.2]. Therapeutic interventions targeting this site include broadly neutralizing monoclonal antibodies like VIS410 and MHAA4549A, as well as experimental small molecules and peptides designed to competitively inhibit the sialic acid interaction [1.3.1, 1.3.5].

Other names

H3 HA receptor-binding siteH3 RBSHemagglutinin H3 receptor-binding siteSialic acid binding siteSialic acid binding pocket

Inhibition of viral attachment to host cell sialic acid receptors by competitive binding or steric hindrance at the receptor-binding site [1.3.1, 1.3.4].