新型冠状病毒的糖基化、糖受体识别及糖链抑制剂的发现  

Glycosylation,glycan receptors recognition of SARS-CoV-2 and discoveries of glycan inhibitors against SARS-CoV-2

作　　者：喻伟艳 许跃强 李建军[2] 李志敏[1] 王琪[3] 杜昱光[2] YU Weiyan;XU Yueqiang;LI Jianjun;LI Zhimin;WANG Qi;DU Yuguang(School of Biological Sciences and Engineering,Jiangxi Agricultural University,Nanchang 330045,Jiangxi,China;State Key Laboratory of Biochemical Engineering,Institute of Processing and Engineering,Chinese Academy of Sciences,Beijing 100190,China;Lung Cancer Translational Medicine Center,The Second Affiliated Hospital of Dalian Medical University,Dalian 116023,Liaoning,China)

机构地区：[1]江西农业大学生物科学与工程学院,江西南昌330045 [2]中国科学院过程工程研究所生化工程国家重点实验室,北京100190 [3]大连医科大学附属第二医院肺癌转化医学中心,辽宁大连116023

出　　处：《生物工程学报》2022年第9期3157-3172,共16页Chinese Journal of Biotechnology

基　　金：国家重点研发计划(2019YFD0902000);大连市呼吸道防护工程研究中心专项基金。

摘　　要：新型冠状病毒疫情(COVID-19)是21世纪截至目前人类面对的最为严重的公共卫生事件。疫苗、中和抗体以及小分子化合药物的出现有效预防和阻止了COVID-19的快速传播,而不断出现的病毒突变体却使这些疫苗及药物的效价降低,这对COVID-19的预防及治疗提出了新的挑战。新型冠状病毒(SARS-CoV-2)通常会先黏附于呼吸道表面的大分子糖链——硫酸乙酰肝素,进而与特异性受体人血管紧张素转化酶2(human angiotensin-converting enzyme 2,hACE2)结合,从而实现对人体的侵入。SARS-CoV-2的刺突(spike,S)蛋白是高度糖基化的,而糖基化对于hACE2与S蛋白的结合也有着重要影响,S蛋白在宿主体内还会被一系列凝集素受体所结合,这意味着糖链在SARS-CoV-2的入侵及感染过程中有着重要的作用。基于SARS-CoV-2的糖基化及糖受体识别机制开发糖链抑制剂可能是预防或治疗新型冠状病毒感染的有效手段,相关研究发现海洋来源的硫酸化多糖、肝素分子及其他的一些糖类具有抗SARS-CoV-2的活性。本文系统阐述了新型冠状病毒的糖基化及其糖链在入侵、感染中的作用,并对抗SARS-CoV-2糖链抑制剂的发现和机制研究现状进行了总结,在此基础上还对糖类抗病毒药物的机遇与挑战进行了展望。COVID-19 represents the most serious public health event in the past few decades of the 21st century.The development of vaccines,neutralizing antibodies,and small molecule chemical agents have effectively prevented the rapid spread of COVID-19.However,the continued emergence of SARS-CoV-2 variants have weakened the efficiency of these vaccines and antibodies,which brought new challenges for searching novel anti-SARS-CoV-2 drugs and methods.In the process of SARS-CoV-2 infection,the virus firstly attaches to heparan sulphate on the cell surface of respiratory tract,then specifically binds to hACE2.The S protein of SARS-CoV-2 is a highly glycosylated protein,and glycosylation is also important for the binding of hACE2 to S protein.Furthermore,the S protein is recognized by a series of lectin receptors in host cells.These finding implies that glycosylation plays important roles in the invasion and infection of SARS-CoV-2.Based on the glycosylation pattern and glycan recognition mechanisms of SARS-CoV-2,it is possible to develop glycan inhibitors against COVID-19.Recent studies have shown that sulfated polysaccharides originated from marine sources,heparin and some other glycans display anti-SARS-CoV-2 activity.This review summarized the function of glycosylation of SARS-CoV-2,discoveries of glycan inhibitors and the underpinning molecular mechanisms,which will provide guidelines to develop glycan-based new drugs against SARS-CoV-2.

关 键 词：新型冠状病毒 糖基化 糖受体 糖链抑制剂 

分 类 号：R914[医药卫生—药物化学]