Synthetic O-Acetyl-N-glycolylneuraminic Acid Oligosaccharides Reveal Host-Associated Binding Patterns of Coronaviral Glycoproteins.

Abstract

A panel of O-acetylated N-glycolylneuraminic acid oligosaccharides has been prepared by diversification of common synthetic precursors by regioselective de-O-acetylation by coronaviral hemagglutinin-esterase (HE) combined with C7-to-C9 acetyl ester migration. The resulting compound library was printed on streptavidin-coated glass slides to give a microarray to investigate receptor binding specificities of viral envelope glycoproteins, including spike proteins and HEs from animal and human coronaviruses. It was found that the binding patterns of the viral proteins for N-glycolylated sialosides differ considerable from those of the previously synthesized N-acetylated counterparts. Generally, the spike proteins tolerate N-glycolyl modification, but selectivities differ among viruses targeting different hosts. On the other hand, the lectin domain of the corresponding HEs showed a substantial decrease or loss of binding of N-glycolylated sialosides. MD simulations indicate that glycolyl recognition by HE is mediated by polar residues in a loop region (109-119) that interacts with the 5-N-glycolyl moiety. Collectively, the results indicate that coronaviruses have adjusted their receptor fine specificities to adapt to the sialoglycome of their host species.