Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

Glycosylation of SARS-CoV-2: structural and functional insights

Journal Article · · Analytical and Bioanalytical Chemistry
 [1];  [2];  [2];  [2];  [2]
  1. Univ. of Georgia, Athens, GA (United States); Complex Carbohydrate Research Center, University of Georgia
  2. Univ. of Georgia, Athens, GA (United States)

The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Similar to other coronaviruses, its particles are composed of four structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. S, E, and M proteins are glycosylated, and the N protein is phosphorylated. The S protein is involved in the interaction with the host receptor human angiotensin-converting enzyme 2 (hACE2), which is also heavily glycosylated. Recent studies have revealed several other potential host receptors or factors that can increase or modulate the SARS-CoV-2 infection. Interestingly, most of these molecules bear carbohydrate residues. While glycans acquired by the viruses through the hijacking of the host machinery help the viruses in their infectivity, they also play roles in immune evasion or modulation. Here, glycans play complex roles in viral pathobiology, both on their own and in association with carrier biomolecules, such as proteins or glycosaminoglycans (GAGs). Understanding these roles in detail can help in developing suitable strategies for prevention and therapy of COVID-19. In this review, we sought to emphasize the interplay of SARS-CoV-2 glycosylated proteins and their host receptors in viral attachment, entry, replication, and infection. Moreover, the implications for future therapeutic interventions targeting these glycosylated biomolecules are also discussed in detail.

Research Organization:
Univ. of Georgia, Athens, GA (United States). Complex Carbohydrate Research Center
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
SC0015662
OSTI ID:
1963808
Journal Information:
Analytical and Bioanalytical Chemistry, Journal Name: Analytical and Bioanalytical Chemistry Journal Issue: 29 Vol. 413; ISSN 1618-2642
Publisher:
SpringerCopyright Statement
Country of Publication:
United States
Language:
English

References (105)

Structural Characterization of N‐Linked Glycans in the Receptor Binding Domain of the SARS‐CoV‐2 Spike Protein and their Interactions with Human Lectins journal October 2020
Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019‐nCoV journal February 2020
Evolutionary dynamics of SARS‐CoV‐2 nucleocapsid protein and its consequences journal November 2020
HumanSARS CoV‐2 spike protein mutations journal January 2021
The epidemiology and clinical information about COVID-19 journal April 2020
A naturally occurring deaminated neuraminic acid, 3-deoxy-D-glycero-D-galacto-nonulosonic acid (KDN). Its unique occurrence at the nonreducing ends of oligosialyl chains in polysialoglycoprotein of rainbow trout eggs. journal September 1986
Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions journal September 2020
Molecular Alterations Prompted by SARS-CoV-2 Infection: Induction of Hyaluronan, Glycosaminoglycan and Mucopolysaccharide Metabolism journal October 2020
Exploitation of glycosylation in enveloped virus pathobiology journal October 2019
Biochemical characterization of SARS-CoV-2 nucleocapsid protein journal June 2020
Dual ELISA using SARS-CoV-2 nucleocapsid protein produced in E. coli and CHO cells reveals epitope masking by N-glycosylation journal January 2021
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor journal April 2020
The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity journal September 2020
SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2 journal November 2020
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein journal December 2020
Targeting host-derived glycans on enveloped viruses for antibody-based vaccine design journal April 2015
How glycobiology can help us treat and beat the COVID-19 pandemic journal January 2021
Virus–Receptor Interactions: The Key to Cellular Invasion journal August 2018
Binding of the SARS-CoV-2 spike protein to glycans journal June 2021
Structure and function of SemiSWEET and SWEET sugar transporters journal August 2015
Effects of Sialic Acid Modifications on Virus Binding and Infection journal December 2016
Glycosylation, ligand binding sites and antigenic variations between membrane glycoprotein of COVID-19 and related coronaviruses journal January 2021
Structural Analysis of Heparin-Derived 3- O -Sulfated Tetrasaccharides: Antithrombin Binding Site Variants journal April 2017
Nanoluciferase complementation-based bioreporter reveals the importance of N-linked glycosylation of SARS-CoV-2 S for viral entry journal June 2021
N- and O-Glycosylation of the SARS-CoV-2 Spike Protein journal January 2021
Mass-Spectrometric Detection of SARS-CoV-2 Virus in Scrapings of the Epithelium of the Nasopharynx of Infected Patients via Nucleocapsid N Protein journal August 2020
Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein journal September 2020
Assessing Antigen Structural Integrity through Glycosylation Analysis of the SARS-CoV-2 Viral Spike journal March 2021
Solution conformations of N-linked oligosaccharides journal October 1987
What it will take to vaccinate the world against COVID-19 journal March 2021
Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus journal November 2003
Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains journal April 2017
Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori journal August 2009
Protein-glycan interactions in the control of innate and adaptive immune responses journal May 2008
Angiotensin-converting enzyme 2 and angiotensin 1–7: novel therapeutic targets journal April 2014
Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy journal September 2016
Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro journal July 2020
Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing journal May 2020
AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells journal January 2021
SARS-CoV-2 membrane glycoprotein M antagonizes the MAVS-mediated innate antiviral response journal October 2020
Vulnerabilities in coronavirus glycan shields despite extensive glycosylation journal May 2020
Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses journal February 2020
A pneumonia outbreak associated with a new coronavirus of probable bat origin journal February 2020
The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice journal May 2020
Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19 journal May 2020
Structural basis for human coronavirus attachment to sialic acid receptors journal June 2019
Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition journal September 2020
Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2 journal April 2021
Heparin and heparan sulfate: structure and function journal March 2002
Investigating changes in the gas-phase conformation of Antithrombin III upon binding of Arixtra using traveling wave ion mobility spectrometry (TWIMS) journal January 2015
Heparin and heparan sulfate: structure and function journal March 2002
Investigating changes in the gas-phase conformation of Antithrombin III upon binding of Arixtra using traveling wave ion mobility spectrometry (TWIMS) journal January 2015
α-glucosidase inhibitors as host-directed antiviral agents with potential for the treatment of COVID-19 journal June 2020
Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis journal February 2006
Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry journal May 2005
Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains journal November 2017
Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein journal September 2017
Human coronaviruses OC43 and HKU1 bind to 9- O -acetylated sialic acids via a conserved receptor-binding site in spike protein domain A journal January 2019
A Human Homolog of Angiotensin-converting Enzyme journal October 2000
Partial Enzymatic Deglycosylation Preserves the Structure of Cleaved Recombinant HIV-1 Envelope Glycoprotein Trimers journal May 2012
Glycosylation of the viral attachment protein of avian coronavirus is essential for host cell and receptor binding journal May 2019
The SARS-CoV-2 envelope and membrane proteins modulate maturation and retention of the spike protein, allowing assembly of virus-like particles journal January 2021
Developments in Mass Spectrometry for Glycosaminoglycan Analysis: A Review journal January 2021
Site-specific N-glycosylation Characterization of Recombinant SARS-CoV-2 Spike Proteins journal January 2021
Deducing the N- and O-glycosylation profile of the spike protein of novel coronavirus SARS-CoV-2 journal May 2020
Identification of 22 N-glycosites on spike glycoprotein of SARS-CoV-2 and accessible surface glycopeptide motifs: Implications for vaccination and antibody therapeutics journal June 2020
Site-specific characterization of SARS-CoV-2 spike glycoprotein receptor-binding domain journal September 2020
Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2 journal October 2020
A proposed role for the SARS‐CoV‐2 nucleocapsid protein in the formation and regulation of biomolecular condensates journal June 2020
SARS-CoV-2 envelope protein topology in eukaryotic membranes journal September 2020
Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus journal March 2006
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation journal February 2020
Site-specific glycan analysis of the SARS-CoV-2 spike journal May 2020
Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2 journal August 2020
Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability journal June 2020
A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2 journal June 2020
Neuropilin-1 is a host factor for SARS-CoV-2 infection journal November 2020
Membrane Protein of Human Coronavirus NL63 Is Responsible for Interaction with the Adhesion Receptor journal October 2019
Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus journal June 2015
HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV journal January 2021
Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives journal January 2021
The Viral Spike Protein Is Not Involved in the Polarized Sorting of Coronaviruses in Epithelial Cells journal January 1998
Role of N-Linked Glycosylation of the Hendra Virus Fusion Protein journal May 2005
N-Glycans on Nipah Virus Fusion Protein Protect against Neutralization but Reduce Membrane Fusion and Viral Entry journal April 2006
Role of N-Linked Glycosylation of the Hendra Virus Fusion Protein journal May 2005
N-Glycans on Nipah Virus Fusion Protein Protect against Neutralization but Reduce Membrane Fusion and Viral Entry journal April 2006
Human Influenza A Virus Hemagglutinin Glycan Evolution Follows a Temporal Pattern to a Glycan Limit journal April 2019
Sars-CoV-2 Envelope and Membrane Proteins: Structural Differences Linked to Virus Characteristics? journal May 2020
A Novel Angiotensin-Converting Enzyme–Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1-9 journal September 2000
A Novel Angiotensin-Converting Enzyme–Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1-9 journal September 2000
The Structure of the Membrane Protein of SARS-CoV-2 Resembles the Sugar Transporter SemiSWEET journal October 2020
Membrane binding proteins of coronaviruses journal April 2019
The Role of Collectins and Galectins in Lung Innate Immune Defense journal September 2018
C-Type Lectin-Like Receptors: Head or Tail in Cell Death Immunity journal February 2020
Human Sialome and Coronavirus Disease-2019 (COVID-19) Pandemic: An Understated Correlation? journal June 2020
Integrative View of the Diversity and Evolution of SWEET and SemiSWEET Sugar Transporters journal December 2017
Can ACE2 Receptor Polymorphism Predict Species Susceptibility to SARS-CoV-2? journal February 2021
Coronaviruses: Is Sialic Acid a Gate to the Eye of Cytokine Storm? From the Entry to the Effects journal August 2020
Glycosylation of Zika Virus is Important in Host–Virus Interaction and Pathogenic Potential journal October 2019
Sialic Acid Receptors: The Key to Solving the Enigma of Zoonotic Virus Spillover journal February 2021
The Hepatitis C Virus Glycan Shield and Evasion of the Humoral Immune Response journal October 2011
Playing Hide and Seek: How Glycosylation of the Influenza Virus Hemagglutinin Can Modulate the Immune Response to Infection journal March 2014
Toward Animal Cell Culture–Based Influenza Vaccine Design: Viral Hemagglutinin N-Glycosylation Markedly Impacts Immunogenicity journal January 2013
COVID ‐19 acute respiratory distress syndrome ( ARDS ): clinical features and differences from typical pre‐ COVID ‐19 ARDS journal June 2020
Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration journal October 2020