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

• Published in: Analytical and bioanalytical chemistry 2021-12, Vol.413 (29), p.7179-7193
• Main Authors: Shajahan, Asif, Pepi, Lauren E., Rouhani, Daniel S., Heiss, Christian, Azadi, Parastoo
• Format: Article
• Language: English
• Subjects: ACE2; Analysis; Analytical Characterization of Viruses; Analytical Chemistry; Angiotensin; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - metabolism; BASIC BIOLOGICAL SCIENCES; Biochemistry; Biomolecules; Carbohydrate Conformation; Carbohydrates; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Composition; Coronaviruses; COVID-19; COVID-19 - virology; envelope protein glycosylation; Food Science; glycosaminoglycan SARS-CoV-2; Glycosaminoglycans; Glycosylation; human ACE2 SARS-CoV-2; Humans; Identification and classification; Infectivity; Laboratory Medicine; membrane protein glycosylation; Monitoring/Environmental Analysis; N protein; Nucleocapsids; Pandemics; Peptidyl-dipeptidase A; Polysaccharides; Polysaccharides - chemistry; Polysaccharides - metabolism; Properties; Protein Conformation; Proteins; Receptors; Respiratory diseases; Review; SARS-CoV-2 - metabolism; SARS-CoV-2 - physiology; SARS-CoV-2 glycosylation; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - metabolism; spike protein glycosylation; Structural proteins; Structure; Structure-function relationships; Therapeutic applications; Viral diseases; Virus attachment; Viruses
• ISSN: 1618-2642; 1618-2650
• DOI: 10.1007/s00216-021-03499-x

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. 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. Graphical abstract