中文
Earlier issues
Announcement
More
Progress in Chemistry 2021, Vol. 33 Issue (4): 524-532 DOI: 10.7536/PC200647 Previous Articles   Next Articles

• Review •

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: Revised: Online: Published:
  • 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)
Richhtml ( 27 ) PDF ( 1206 ) Cited
Export

EndNote

Ris

BibTeX

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
Fig.1 Classification of coronavirus
Fig.2 Structure and infection mechanism of SARS-CoV-2
Fig.3 Biosynthetic pathways for N-linked glycosylation and O-linked glycosylation
Fig.4 Glycosylation of SARS-CoV-2 S protein
Fig.5 Antiviral compounds that interfere with glycosylation and their chemical structures
[1]
Payne S. Viruses. Amsterdam: Elsevier, 2017.149.
[2]
Su S, Wong G, Shi W F, Liu J, Lai A C K, Zhou J Y, Liu W J, Bi Y H, Gao G F. Trends Microbiol., 2016, 24(6): 490.

pmid: 27012512
[3]
Li S W, Lin C W. BioMedicine, 2013, 3(1): 43.

pmid: 32289002
[4]
Ceraolo C, Giorgi F M. J. Med. Virol., 2020, 92(5): 522.

doi: 10.1002/jmv.25700 pmid: 32027036
[5]
Shi S B, Qin M, Shen B, Cai Y L, Liu T, Yang F, Gong W, Liu X, Liang J J, Zhao Q Y, Huang H, Yang B, Huang C X. JAMA Cardiol., 2020, 5(7): 802.

pmid: 32211816
[6]
Mao L, Jin H J, Wang M D, Hu Y, Chen S C, He Q W, Chang J, Hong C D, Zhou Y F, Wang D, Miao X P, Li Y N, Hu B. JAMA Neurol., 2020, 77(6): 683.

doi: 10.1001/jamaneurol.2020.1127 pmid: 32275288
[7]
Diao B, Wang C, Wang R, Feng Z, Tan Y, Wang H, Wang C, Liu L, Liu Y, Liu Y, Wang G, Yuan Z, Ren L, Wu Y, and Chen Y. medRxiv, 2020, DOI: 10.1101/2020.03.04.20031120.

pmid: 33880484
[8]
Xiao F, Tang M W, Zheng X B, Liu Y, Li X F, Shan H. Gastroenterology, 2020, 158(6): 1831.

pmid: 32142773
[9]
Klok F A, Kruip M J H A, van der Meer N J M, Arbous M S, Gommers D, Kant K M, Kaptein F H J, van Paassen J, Stals M A M, Huisman M V, Endeman H. Thromb. Res., 2020, 191: 148.

pmid: 32381264
[10]
Li G, Fan Y H, Lai Y N, Han T T, Li Z H, Zhou P W, Pan P, Wang W B, Hu D W, Liu X H, Zhang Q W, Wu J G. J. Med. Virol., 2020, 92(4): 424.

pmid: 31981224
[11]
Li W H, Moore M J, Vasilieva N, Sui J H, Wong S K, Berne M A, Somasundaran M, Sullivan J L, Luzuriaga K, Greenough T C, Choe H, Farzan M. Nature, 2003, 426(6965): 450.

pmid: 14647384
[12]
Glowacka I, Bertram S, Muller M A, Allen P, Soilleux E, Pfefferle S, Steffen I, Tsegaye T S, He Y, Gnirss K, Niemeyer D, Schneider H, Drosten C, Pohlmann S. J. Virol., 2011, 85(9): 4122.

pmid: 21325420
[13]
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens T S, Herrler G, Wu N H, Nitsche A, Müller M A, Drosten C, Pöhlmann S. Cell, 2020, 181(2): 271.

pmid: 32142651
[14]
Raj V S, Mou H H, Smits S L, Dekkers D H W, Müller M A, Dijkman R, Muth D, Demmers J A A, Zaki A, Fouchier R A M, Thiel V, Drosten C, Rottier P J M, Osterhaus A D M E, Bosch B J, Haagmans B L. Nature, 2013, 495(7440): 251. 50fba2c4-d237-44c2-a8be-f73aceb241f2

doi: 10.1038/nature12005
[15]
Wu F, Zhao S, Yu B, Chen Y M, Wang W, Song Z G, Hu Y, Tao Z W, Tian J H, Pei Y Y, Yuan M L, Zhang Y L, Dai F H, Liu Y, Wang Q M, Zheng J J, Xu L, Holmes E C, Zhang Y Z. Nature, 2020, 579(7798): 265.

pmid: 32015508
[16]
Zhou P, Yang X L, Wang X G, Hu B, Zhang L, Zhang W, Si H R, Zhu Y, Li B, Huang C L, Chen H D, Chen J, Luo Y, Guo H, Jiang R D, Liu M Q, Chen Y, Shen X R, Wang X, Zheng X S, Zhao K, Chen Q J, Deng F, Liu L L, Yan B, Zhan F X, Wang Y Y, Xiao G F, Shi Z L. Nature, 2020, 579(7798): 270.

pmid: 32015507
[17]
Wrapp D, Wang N S, Corbett K S, Goldsmith J A, Hsieh C L, Abiona O, Graham B S, McLellan J S. Science, 2020, 367(6483): 1260.

doi: 10.1126/science.abb2507 pmid: 32075877
[18]
Chen Y, Guo Y, Pan Y H, Zhao Z J. Biochem. Biophys. Res. Commun., 2020, 525(1): 135.

doi: 10.1016/j.bbrc.2020.02.071
[19]
Walls A C, Tortorici M A, Bosch B J, Frenz B, Rottier P J M, DiMaio F, Rey F A, Veesler D. Nature, 2016, 531(7592): 114.

pmid: 26855426
[20]
Belouzard S, Chu V C, Whittaker G R. PNAS, 2009, 106(14): 5871.

doi: 10.1073/pnas.0809524106 pmid: 19321428
[21]
Millet J K, Whittaker G R. PNAS, 2014, 111(42): 15214.

pmid: 25288733
[22]
Walls A C, Park Y J, Tortorici M A, Wall A, McGuire A T, Veesler D. Cell, 2020, 183(6): 1735.

doi: 10.1016/j.cell.2020.11.032 pmid: 33306958
[23]
Xiang T, Zhang X L. Prog. Biochem. Biophys., 2017, 44(10): 898.
向田, 章晓联. 生物化学与生物物理进展, 2017, 44(10): 898.
[24]
Vigerust D J, Shepherd V L. Trends Microbiol., 2007, 15(5): 211. 2495ce6b-296e-4742-bca8-92930c351764

doi: 10.1016/j.tim.2007.03.003
[25]
Watanabe Y, Bowden T A, Wilson I A, Crispina M. Biochim. Biophys. Acta Gen. Subj., 2019, 1863(10): 1480.

doi: 10.1016/j.bbagen.2019.05.012 pmid: 31121217
[26]
Ying W T, Hao Y W, Zhang Y J, Peng W M, Qin E D, Cai Y, Wei K H, Wang J, Chang G H, Sun W, Dai S J, Li X H, Zhu Y P, Li J Q, Wu S F, Guo L H, Dai J Q, Wang J L, Wan P, Chen T G, Du C J, Li D, Wan J, Kuai X Z, Li W H, Shi R, Wei H D, Cao C, Yu M, Liu H, Dong F T, Wang D G, Zhang X M, Qian X H, Zhu Q Y, He F C. Proteomics, 2004, 4(2): 492.

doi: 10.1002/pmic.200300676 pmid: 14760722
[27]
Krokhin O, Li Y, Andonov A, Feldmann H, Flick R, Jones S, Stroeher U, Bastien N, Dasuri K V N, Cheng K D, Simonsen J N, Perreault H, Wilkins J, Ens W, Plummer F, Standing K G. Mol. Cell. Proteom., 2003, 2(5): 346.

doi: 10.1074/mcp.M300048-MCP200
[28]
Han D P, Lohani M, Cho M W. J. Virol., 2007, 81(21): 12029.

doi: 10.1128/JVI.00315-07 pmid: 17715238
[29]
Watanabe Y, Allen J D, Wrapp D, McLellan J S, Crispin M. Science, 2020, 369(6501): 330.

doi: 10.1126/science.abb9983 pmid: 32366695
[30]
Zhang Y, Zhao W, Mao Y, Wang S, Zhong Y, Su T, Gong M, Lu X, Cheng J, Yang H. bioRxiv, 2020,April 19.
[31]
Shajahan A, Supekar N T, Gleinich A S, Azadi P. Glycobiology, 2020, 30(12): 981.

pmid: 32363391
[32]
Andersen K G, Rambaut A, Lipkin W I, Holmes E C, Garry R F. Nat. Med., 2020, 26(4): 450.

pmid: 32284615
[33]
Walls A C, Tortorici M A, Frenz B, Snijder J, Li W T, Rey F A, DiMaio F, Bosch B J, Veesler D. Nat. Struct. Mol. Biol., 2016, 23(10): 899.

doi: 10.1038/nsmb.3293 pmid: 27617430
[34]
Han D P, Kim H G, Kim Y B, Poon L L M, Cho M W. Virology, 2004, 326(1): 140.

pmid: 15262502
[35]
Zhou Y C, Lu K, Pfefferle S, Bertram S, Glowacka I, Drosten C, Pohlmann S, Simmons G. J. Virol., 2010, 84(17): 8753.

pmid: 20573835
[36]
Li W T, Hulswit R J G, Widjaja I, Raj V S, McBride R, Peng W J, Widagdo W, Tortorici M A, van Dieren B, Lang Y F, van Lent J W M, Paulson J C, de Haan C A M, de Groot R J, van Kuppeveld F J M, Haagmans B L, Bosch B J. PNAS, 2017, 114(40): E8508.

doi: 10.1073/pnas.1712592114 pmid: 28923942
[37]
Gheblawi M, Wang K M, Viveiros A, Nguyen Q, Zhong J C, Turner A J, Raizada M K, Grant M B, Oudit G Y. Circ. Res., 2020, 126(10): 1456.

doi: 10.1161/CIRCRESAHA.120.317015 pmid: 32264791
[38]
Yan R H, Zhang Y Y, Li Y N, Xia L, Guo Y Y, Zhou Q. Science, 2020, 367(6485): 1444.

pmid: 32132184
[39]
Shajahan A, Archer-Hartmann S, Supekar N T, Gleinich A S, Heiss C, Azadi P. bioRxiv, 2020,DOI:10.1101/2020.05.01.071688.
[40]
Mehdipour A R, Hummer G. bioRxiv, 2020, DOI: 10.1101/2020.07.09.193680.

pmid: 33880470
[41]
Zheng L, Zhang P, Wang Q, Lai F C. Chin. J. Blood Transfus., 2006, 19(1): 80.
郑磊, 张鹏, 王前, 赖福才. 中国输血杂志, 2006, 19(1): 80.
[42]
Gong X M, Xu J Y, Ding Y L. Progress in Pharmaceutical Sciences, 2002,(5): 266.
龚晓明, 许激扬, 丁玉林. 药学进展, 2002,(5): 266.
[43]
Zhao X S, Guo F, Comunale M A, Mehta A, Sehgal M, Jain P, Cuconati A, Lin H X, Block T M, Chang J H, Guo J T. Antimicrob. Agents Chemother., 2015, 59(1): 206.

doi: 10.1128/AAC.03999-14 pmid: 25348530
[44]
Huang M X, Li M, Xiao F, Pang P F, Liang J B, Tang T T, Liu S X, Chen B H, Shu J X, You Y Y, Li Y, Tang M W, Zhou J H, Jiang G M, Xiang J F, Hong W X, He S M, Wang Z Q, Feng J H, Lin C Q, Ye Y N, Wu Z L, Li Y C, Zhong B, Sun R L, Hong Z S, Liu J, Chen H L, Wang X H, Li Z H, Pei D Q, Tian L, Xia J Y, Jiang S P, Zhong N S, Shan H. National Science Review, 2020, 7(9): 1428.

doi: 10.1093/nsr/nwaa113
[45]
Vincent M J, Bergeron E, Benjannet S, Erickson B R, Rollin P E, Ksiazek T G, Seidah N G, Nichol S T. Virol. J., 2005, 2(1): 69.
[46]
Li Z H, Li T H, Dai S X, Xie X L, Ma X F, Zhao W, Zhang W M, Li J, Wang P G. ChemBioChem, 2013, 14(10): 1239. f3712739-dd37-443a-ba6d-ae060ada32db

doi: 10.1002/cbic.201300197
[47]
Li T H, Guo L N, Zhang Y, Wang J J, Li Z H, Lin L, Zhang Z X, Li L, Lin J P, Zhao W, Li J, Wang P G. Carbohydr. Res., 2011, 346(9): 1083.

pmid: 21514574
[1] Jiali Wang, Ling Zhu, Chen Wang, Shengbin Lei, Yanlian Yang. Nanotechnology for Detection of Circulating Tumor Cells and Extracellular Vesicles [J]. Progress in Chemistry, 2022, 34(1): 178-197.
[2] Huifeng Xu, Yongqiang Dong, Xi Zhu, Lishuang Yu. Novel Two-Dimensional MXene for Biomedical Applications [J]. Progress in Chemistry, 2021, 33(5): 752-766.
[3] Jiajia Wang, Huiying Wu, Renfeng Dong, Yuepeng Cai. Micro/Nanomotors on the Way to Intelligent Cancer Diagnosis, Delivery and Therapy [J]. Progress in Chemistry, 2021, 33(5): 883-894.
[4] Yan Huang, Guodong Liu, Xueji Zhang. Detection and Diagnosis of COVID-19 [J]. Progress in Chemistry, 2020, 32(9): 1241-1251.
[5] Hanyu Zhang, Meng Liu, Xia Wu, Miao Liu, Decai Xiong, Xinshan Ye. Photo-/Electro-Driven Carbohydrate-Based Reactions [J]. Progress in Chemistry, 2020, 32(11): 1804-1823.
[6] Axin Liang, Bo Tang, Liquan Sun, Xin Zhang, Huipeng Hou, Aiqin Luo. New Materials for the Separation and Enrichment of N-Glycopeptides/Glycoproteins [J]. Progress in Chemistry, 2019, 31(7): 996-1006.
[7] Jun Hu, Yuzhu Yao, Yanxiao Ao, Hai Yang, Xiangliang Yang*, Huibi Xu. Inorganic Nanomaterials for Tumor Comprehensive Therapy [J]. Progress in Chemistry, 2018, 30(10): 1584-1591.
[8] Huang Di, Xiang Nan, Tang Wenlai, Zhang Xinjie, Ni Zhonghua. Microfluidics-Based Circulating Tumor Cells Separation [J]. Progress in Chemistry, 2015, 27(7): 882-912.
[9] Li Wenwen, Duan Yixiang. Human Exhaled Breath Analysis: Trends in Techniques and Its Potential Applications in Non-Invasive Clinical Diagnosis [J]. Progress in Chemistry, 2015, 27(4): 321-335.
[10] Zeng Feng, Pan Zhenzhen, Zhang Meng, Huang Yongzhuo, Cui Yanna, Xu Qin. Preparation and Application of Ordered Mesoporous Silica Nanoparticles in the Therapy and Diagnosis of Tumor [J]. Progress in Chemistry, 2015, 27(10): 1356-1373.
[11] Song Chunyuan, Chen Wenqiang, Yang Yanjun, Yang Boyue, Su Shao, Wang Lianhui. Surface-Enhanced Raman Scattering Tags Used in Cell Recognition, Imaging, Diagnosis and Treatment [J]. Progress in Chemistry, 2015, 27(1): 91-102.
[12] Tao Niu, Ming Hu. Microbiota Structures, Human Health and Cancer Chemoprevention [J]. Progress in Chemistry, 2013, 25(09): 1601-1612.
[13] Cai Xiaohui, Shi Lin, Liu Xingfen*, Huang Yanqin, Fan Quli, Huang Wei*. Functionalized Conjugated Polymers and Their Application in the Biological and/or Chemical Analysis [J]. Progress in Chemistry, 2013, 25(06): 975-989.
[14] Zhang Jinchao*, Hu Yi*, Yu Siwang, Gao Yuxi, Zhang Haisong. The Study of Biological Inorganic Chemistry Problemsin Translational Medicine [J]. Progress in Chemistry, 2013, 25(04): 469-478.
[15] Chen Hongzhang, Peng Xiaowei. Steam Explosion Technology Applied to High-Value Utilization of Herb Medicine Resources [J]. Progress in Chemistry, 2012, (9): 1857-1864.