Site-specific glycan analysis of the SARS-CoV-2 spike

• Published in: Science (American Association for the Advancement of Science) Vol. 369; no. 6501; pp. 330 - 333
• Main Authors: Watanabe, Yasunori, Allen, Joel D, Wrapp, Daniel, McLellan, Jason S, Crispin, Max
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 17.07.2020; American Association for the Advancement of Science
• Subjects: Antibiotics; Antibodies; Antigens; Betacoronavirus - chemistry; Binding Sites; Biochem; Cell fusion; Coronaviridae; Coronavirus Infections; Coronaviruses; COVID-19; Glycan; Glycopeptides; Glycopeptides - chemistry; Glycopeptides - immunology; Glycoproteins; Glycosylation; Humans; Immune response; Immune response (humoral); Immune system; Mapping; Mass Spectrometry; Mass spectroscopy; Membrane fusion; Microbio; Models, Molecular; Neutralization; Oligosaccharides - chemistry; Pandemics; Pneumonia, Viral; Polysaccharides; Polysaccharides - chemistry; Protein folding; Protein Structure, Tertiary; Proteins; Recombinant Proteins - chemistry; Recombinant Proteins - immunology; Respiratory diseases; S gene; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; Spike protein; Trimers; Vaccine development; Vaccines; Viral diseases; Viruses
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abb9983

The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion. The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.