Synthetic O-acetylated sialosides facilitate functional receptor identification for human respiratory viruses

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 alpha 2,8-linked disialoside. Immunofluorescence and cell entry studies support that such a glycotope as part of a ganglioside is a functional receptor for human coronaviruses.

Automated summary

The study found specificities of human and animal viruses in binding to O-acetylated sialic acid. A chemoenzymatic methodology was developed to provide almost any sialate-acetylation pattern, and a microarray of O-acetylated sialoglycans was used to determine receptor specificity. Host-specific patterns of receptor recognition were observed, with human coronaviruses found to uniquely bind to a specific glycotope as part of a ganglioside.