荷兰乌得勒支大学Geert-Jan Boons团队报道了合成-O乙酰化唾液酸苷及其乙酰氨基脱氧类似物作为冠状病毒血凝素酯酶识别探针。相关研究成果发表在2021年12月30日出版的国际知名学术期刊《美国化学会杂志》。

O-乙酰化是唾液酸的一种常见修饰，可以发生在碳4-，碳7-，碳8-和/或碳9上。乙酰化唾液糖苷作为受体被几种β冠状病毒和环状病毒以及流感病毒C和D所利用。这些病毒识别特定O-乙酰化唾液酸苷的分子基础尚不清楚，也不清楚病毒是如何进化来识别其宿主表达的特定O-乙酰化唾液酸苷的。

该文中，研究人员描述了一种化学酶方法，该方法可以容易地提供唾液聚糖类似物，其中C4和/或C7处的乙酰酯被稳定的乙酰胺部分取代。这些类似物及其天然对应物用于检测冠状病毒血凝素酯酶（HEs）凝集素结构域的配体需求。结果表明，针对不同宿主物种的病毒的HEs对O-乙酰化有不同的要求。

它还表明，酯-酰胺扰动导致结合减少或丧失。BCoV的HE与乙酰氨基类似物和天然对应物的STD NMR和分子模拟表明，结合受唾液酸苷的乙酰部分和凝集素的疏水斑块之间的互补性控制。这些元素的精确空间排列是重要的，酯-酰胺微扰会导致大量结合丧失。感染其他物种的冠状病毒HEs的分子动力学模拟表明，这些病毒通过加入疏水或亲水元素来调节乙酰酯识别，从而调整其HE特异性。

附：英文原文

Title: Synthetic O-Acetylated Sialosides and their Acetamido-deoxy Analogues as Probes for Coronaviral Hemagglutinin-esterase Recognition

Author: Zeshi Li, Luca Unione, Lin Liu, Yifei Lang, Robert P. de Vries, Raoul J. de Groot, Geert-Jan Boons

Issue&Volume: December 30, 2021

Abstract: O-Acetylation is a common modification of sialic acids that can occur at carbons 4-, 7-, 8-, and/or 9. Acetylated sialosides are employed as receptors by several betacoronaviruses and toroviruses, and by influenza C and D viruses. The molecular basis by which these viruses recognize specific O-acetylated sialosides is poorly understood, and it is unknown how viruses have evolved to recognize specific O-acetylated sialosides expressed by their host. Here, we describe a chemoenzymatic approach that can readily provide sialoglycan analogues in which acetyl esters at C4 and/or C7 are replaced by stabilizing acetamide moieties. The analogues and their natural counterparts were used to examine the ligand requirements of the lectin domain of coronaviral hemagglutinin-esterases (HEs). It revealed that HEs from viruses targeting different host species exhibit different requirements for O-acetylation. It also showed that ester-to-amide perturbation results in decreased or loss of binding. STD NMR and molecular modeling of the complexes of the HE of BCoV with the acetamido analogues and natural counterparts revealed that binding is governed by the complementarity between the acetyl moieties of the sialosides and the hydrophobic patches of the lectin. The precise spatial arrangement of these elements is important, and an ester-to-amide perturbation results in substantial loss of binding. Molecular Dynamics simulations with HEs from coronaviruses infecting other species indicate that these viruses have adapted their HE specificity by the incorporation of hydrophobic or hydrophilic elements to modulate acetyl ester recognition.

DOI: 10.1021/jacs.1c10329

Source: https://pubs.acs.org/doi/10.1021/jacs.1c10329