The bulky and the sweet: How neutralizing antibodies and glycan receptors compete for virus binding.

Abstract

Numerous viruses rely on glycan receptor binding as the initial step in host cell infection. Engagement of specific glycan receptors such as sialylated carbohydrates, glycosaminoglycans, or histo‐blood group antigens can determine host range, tissue tropism, and pathogenicity. Glycan receptor‐binding sites are typically located in exposed regions on viral surfaces—sites that are also generally prone to binding of neutralizing antibodies that directly interfere with virus‐glycan receptor interactions. In this review, we examine the locations and architecture of the glycan‐ and antibody‐binding sites in four different viruses with stalk‐like attachment proteins (reovirus, influenza virus, norovirus, and coronavirus) and investigate the mechanisms by which antibodies block glycan recognition. Those viruses exemplify that direct molecular mimicking of glycan receptors by antibodies is rare and further demonstrate that antibodies often partly overlap or bind sufficiently close to the receptor‐binding region to hinder access to this site, achieving neutralization partially because of the epitope location and partly due to their sheer size.