Glycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study

doi:10.3390/biom11111586

	Glycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study
	Gao, Meina 1,2; Li, Hui 2,3,4; Ye, Chenghao 5; Chen, Kaixian 1,2,3; Jiang, Hualiang 1,2,3,4; Yu, Kunqian 2,3
刊名	BIOMOLECULES
	2021-11-01
卷号	11 期号:11 页码:16
关键词	DC-SIGN glycan epitopes carbohydrate recognition mechanism natural glycoside antagonists molecular dynamics simulations COVID-19
DOI	10.3390/biom11111586
通讯作者	Yu, Kunqian(yukunqian@simm.ac.cn)
英文摘要	Glycosylation is an important post-translational modification that affects a wide variety of physiological functions. DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) is a protein expressed in antigen-presenting cells that recognizes a variety of glycan epitopes. Until now, the binding of DC-SIGN to SARS-CoV-2 Spike glycoprotein has been reported in various articles and is regarded to be a factor in systemic infection and cytokine storm. The mechanism of DC-SIGN recognition offers an alternative method for discovering new medication for COVID-19 treatment. Here, we discovered three potential pockets that hold different glycan epitopes by performing molecular dynamics simulations of previously reported oligosaccharides. The "EPN " motif, "NDD " motif, and Glu354 form the most critical pocket, which is known as the Core site. We proposed that the type of glycan epitopes, rather than the precise amino acid sequence, determines the recognition. Furthermore, we deduced that oligosaccharides could occupy an additional site, which adds to their higher affinity than monosaccharides. Based on our findings and previously described glycoforms on the SARS-CoV-2 Spike, we predicted the potential glycan epitopes for DC-SIGN. It suggested that glycan epitopes could be recognized at multiple sites, not just Asn234, Asn149 and Asn343. Subsequently, we found that Saikosaponin A and Liquiritin, two plant glycosides, were promising DC-SIGN antagonists in silico.
资助项目	National Key R & D Program of China[2020YFC0841400] ; Shanghai Municipal Science and Technology Major Project ; National Natural Science Foundation of China[81773634] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2018ZX09711002] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDPB2505]
WOS关键词	CARBOHYDRATE-RECOGNITION ; BINDING ; PROTEIN ; INFECTION ; PARAMETERS ; RECEPTOR ; MMGBSA
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	MDPI
WOS记录号	WOS:000724031000001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/299018]
专题	中国科学院上海药物研究所
通讯作者	Yu, Kunqian
作者单位	1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 200031, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai Inst Adv Immunochem Studies, Shanghai 200031, Peoples R China 5.Shantou Univ, Dept Chem, Shantou 515063, Peoples R China
推荐引用方式 GB/T 7714	Gao, Meina,Li, Hui,Ye, Chenghao,et al. Glycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study[J]. BIOMOLECULES,2021,11(11):16.
APA	Gao, Meina,Li, Hui,Ye, Chenghao,Chen, Kaixian,Jiang, Hualiang,&Yu, Kunqian.(2021).Glycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study.BIOMOLECULES,11(11),16.
MLA	Gao, Meina,et al."Glycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study".BIOMOLECULES 11.11(2021):16.