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

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.