LAUSR

The transmission of viruses from animal reservoirs to humans poses major threats to public health. Preparedness for future zoonotic outbreaks requires a fundamental understanding of how viruses of animal origin have adapted to binding to a cell surface component and/or receptor of the new host. Here we report on the specificities of human and animal viruses that engage with O -acetylated sialic acid, which include betacoronaviruses, toroviruses and influenza C and D viruses. Key to these studies was the development of a chemoenzymatic methodology that can provide almost any sialate-acetylation pattern. A collection of O -acetylated sialoglycans was printed as a microarray for the determination of receptor specificity. These studies showed host-specific patterns of receptor recognition and revealed that three distinct human respiratory viruses uniquely bind 9- O -acetylated α2,8-linked disialoside. Immunofluorescence and cell entry studies support that such a glycotope as part of a ganglioside is a functional receptor for human coronaviruses. The specificity of human and animal viruses that engage with O -acetylated sialic acids has now been probed using a collection of O -acetylated sialoglycans obtained by diversification of trisaccharide precursors with viral haemagglutinin–esterases. The results revealed host-specific patterns of receptor recognition and showed that human respiratory viruses uniquely employ 9- O -acetylated α2,8-linked disialosides as receptors.