Synthetic O-acetylated sialosides facilitate functional receptor identification for human respirator

Abstract

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.

Cite this article

Li, Z., Lang, Y., Liu, L. et al. Synthetic O-acetylated sialosides facilitate functional receptor identification for human respiratory viruses. Nat. Chem. (2021). https://doi.org/10.1038/s41557-021-00655-9

View full text

>> Full Text:   Synthetic O-acetylated sialosides facilitate functional receptor identification for human respirator