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

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 epito...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Meina Gao, Hui Li, Chenghao Ye, Kaixian Chen, Hualiang Jiang, Kunqian Yu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	DC-SIGN glycan epitopes carbohydrate recognition mechanism natural glycoside antagonists molecular dynamics simulations COVID-19 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c80eeb5284d540d680c15d276853f1b6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c80eeb5284d540d680c15d276853f1b6
record_format	dspace
spelling	oai:doaj.org-article:c80eeb5284d540d680c15d276853f1b62021-11-25T16:52:28ZGlycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study10.3390/biom111115862218-273Xhttps://doaj.org/article/c80eeb5284d540d680c15d276853f1b62021-10-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1586https://doaj.org/toc/2218-273XGlycosylation 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.Meina GaoHui LiChenghao YeKaixian ChenHualiang JiangKunqian YuMDPI AGarticleDC-SIGNglycan epitopescarbohydrate recognition mechanismnatural glycoside antagonistsmolecular dynamics simulationsCOVID-19MicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1586, p 1586 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	DC-SIGN glycan epitopes carbohydrate recognition mechanism natural glycoside antagonists molecular dynamics simulations COVID-19 Microbiology QR1-502
spellingShingle	DC-SIGN glycan epitopes carbohydrate recognition mechanism natural glycoside antagonists molecular dynamics simulations COVID-19 Microbiology QR1-502 Meina Gao Hui Li Chenghao Ye Kaixian Chen Hualiang Jiang Kunqian Yu Glycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study
description	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.
format	article
author	Meina Gao Hui Li Chenghao Ye Kaixian Chen Hualiang Jiang Kunqian Yu
author_facet	Meina Gao Hui Li Chenghao Ye Kaixian Chen Hualiang Jiang Kunqian Yu
author_sort	Meina Gao
title	Glycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study
title_short	Glycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study
title_full	Glycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study
title_fullStr	Glycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study
title_full_unstemmed	Glycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study
title_sort	glycan epitopes and potential glycoside antagonists of dc-sign involved in covid-19: in silico study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c80eeb5284d540d680c15d276853f1b6
work_keys_str_mv	AT meinagao glycanepitopesandpotentialglycosideantagonistsofdcsigninvolvedincovid19insilicostudy AT huili glycanepitopesandpotentialglycosideantagonistsofdcsigninvolvedincovid19insilicostudy AT chenghaoye glycanepitopesandpotentialglycosideantagonistsofdcsigninvolvedincovid19insilicostudy AT kaixianchen glycanepitopesandpotentialglycosideantagonistsofdcsigninvolvedincovid19insilicostudy AT hualiangjiang glycanepitopesandpotentialglycosideantagonistsofdcsigninvolvedincovid19insilicostudy AT kunqianyu glycanepitopesandpotentialglycosideantagonistsofdcsigninvolvedincovid19insilicostudy
_version_	1718412922743422976

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

Ejemplares similares