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化学进展 2021, Vol. 33 Issue (4): 524-532 DOI: 10.7536/PC200647 前一篇   后一篇

• 综述 •

糖基化在新型冠状病毒侵染中的机制及药物研发中的应用

刘文杰1, 刘凯会1, 张彦伟1, 王良1, 张梦裔1,*(), 李静1,*()   

  1. 1 南开大学药学院和药物化学生物学国家重点实验室 南开大学化学学院和天津化学化工协同创新中心 天津 300071
  • 收稿日期:2020-06-15 修回日期:2020-07-16 出版日期:2021-04-20 发布日期:2020-12-22
  • 通讯作者: 张梦裔, 李静
  • 基金资助:
    北京分子科学国家研究中心开放课题(BNLMS201826); ,南开大学中央高校基本科研业务费专项资金(63201105); 国家自然科学基金项目(82073879); 国家自然科学基金项目(81573282); 国家自然科学基金项目(U1801288)
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The Mechanism of Glycosylation in SARS-CoV-2 Infection and Application in Drug Development

Wenjie Liu1, Kaihui Liu1, Yanwei Zhang1, Liang Wang1, Mengyi Zhang1(), Jing Li1()   

  1. 1 College of Pharmacy & The State Key Laboratory of Medicinal Chemical Biology, College of Chemistry & The National Collaborative Innovation Centre of Chemical Science and Engineering, Nankai University, Tianjin 300071, China
  • Received:2020-06-15 Revised:2020-07-16 Online:2021-04-20 Published:2020-12-22
  • Contact: Mengyi Zhang, Jing Li
  • Supported by:
    the Open Fund of Beijing Molecular Science National Research Center(BNLMS201826); the Basic Research Funds for Central Universities(63201105); and National Natural Science Foundation of China(82073879); and National Natural Science Foundation of China(81573282); and National Natural Science Foundation of China(U1801288)

冠状病毒(Coronavirus, CoV)是一类具有包膜的正股单链RNA病毒,可感染人类和多种动物。2019年末,一种新的β-冠状病毒SARS-CoV-2(Severe acute respiratory syndrome-coronavirus-2)开始在人际间传播,该病毒引发的疾病“COVID-19”(Coronavirus disease 2019)对全球公共卫生构成严重威胁。糖基化是一种存在于蛋白质上的翻译后修饰,可影响蛋白质的折叠、稳定性及和受体之间的结合等,研究表明SARS-CoV-2包膜中的病毒嗜性决定因子-刺突蛋白(Spike,S)及宿主细胞上的主要受体血管紧张素转化酶2(Angiotensin-converting enzyme 2, ACE2)均为高度糖基化蛋白。为探明糖基化修饰在SARS-CoV-2病毒侵染及与宿主免疫应答中的作用,本文综述了该病毒的侵染机制,体外重组病毒S蛋白和宿主受体ACE2的糖基化类型及糖基化对病毒与宿主相互作用的影响,并提出基于糖基化的COVID-19诊断和药物研发新策略。

关键词： 新型冠状病毒, 糖基化, 刺突蛋白, 诊断, 抗病毒药物

Coronavirus(CoV) is a class of enveloped, positive-sense single-stranded RNA viruses which can infect humans and animals. At the end of 2019, a novel β-coronavirus SARS-CoV-2(Severe acute respiratory syndrome-coronavirus-2) has started to spread from person to person, and the virus-related disease "COVID-19"(Coronavirus disease 2019) poses a serious threat to global public health in different countries. Glycosylation is a post-translational modification that exists on proteins, which can affect the protein folding, stability, and the binding between virus and host receptors. Spike(S) protein determines the tropism of the virus to the host. A plenty of studies have shown that the spike(S) protein in the SARS-CoV-2 envelope and the main receptor on the host cell, Angiotensin converting enzyme 2(ACE2), are highly glycosylated proteins. To explore the role of glycosylation in virus infection and host immune response, this review summarizes the infection mechanism of SARS-CoV-2, the glycosylation modifications of recombinant S protein and host receptor protein ACE2, and the effects of glycosylation on the interaction between virus and host cells. Finally, based on the mechanism of glycosylation, we propose novel potential strategies for COVID-19 diagnosis and anti-virus drug development, which provides new directions for the diagnosis and treatment of COVID-19.

Contents

1 Introduction

2 The infection mechanism of SARS-CoV-2

3 S protein: highly glycosylated viral tropic protein

3.1 Viral glycosylation mechanism: host-dependent glycosylation modification system

3.2 Subtypes of glycosylation and the related sites

3.3 The role of viral protein glycosylation

4 Glycosylation modification of host receptor protein ACE2

5 SARS-CoV-2 detection and drug intervention strategies based on glycosylation

5.1 Development of efficient and sensitive kits using agglutination

5.2 Drugs that affects glycosylation

6 Conclusion and outlook

Key words: novel coronavirus, glycosylation, Spike protein, diagnosis, anti-virus drug
()
图1 冠状病毒的分类
Fig.1 Classification of coronavirus
图2 新型冠状病毒的结构及入侵机制
Fig.2 Structure and infection mechanism of SARS-CoV-2
图3 N-连接糖基化和O-连接糖基化的生物合成途径
Fig.3 Biosynthetic pathways for N-linked glycosylation and O-linked glycosylation
图4 SARS-CoV-2 S蛋白的糖基化
Fig.4 Glycosylation of SARS-CoV-2 S protein
图5 干扰糖基化的抗病毒化合物及其化学结构
Fig.5 Antiviral compounds that interfere with glycosylation and their chemical structures
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