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

By Yasunori Watanabe, Joel D. Allen, D. Wrapp, J. McLellan, M. Crispin. 2020

1,433 citations recorded by the source corpus.

SARS-CoV-2 spike protein, elaborated Vaccine development for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on the trimeric spike protein that initiates infection. Each protomer in the trimeric spike has 22 glycosylation sites. How these sites are glycosylated may affect which cells the virus can infect and could shield some epitopes from antibody neutralization. Watanabe et al. expressed and purified recombinant glycosylated spike trimers, proteolysed them to yield glycopeptides containing a single glycan, and determined the composition of the glycan sites by mass spectrometry. The analysis provides a benchmark that can be used to measure antigen quality as vaccines and antibody tests are developed. Science this issue p. 330 A mass spectrometry analysis reveals the glycan composition at all glycosylation sites on the SARS-CoV-2 spike protein. 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.

Subfields: Ecology, Infectious Diseases, Radiology, Nuclear Medicine and Imaging

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Ecology

1. Neil P. King
2. Cameron Martino

In Infectious Diseases

1. D. Veesler
2. A. Walls
3. Ralph S. Baric
4. Abdo A. Elfiky

In Radiology, Nuclear Medicine and Imaging

1. Neil P. King
2. Dina Schneidman-Duhovny
3. Haim J. Wolfson
4. Yigong Shi
5. J. Esko

Citations in the corpus

• Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, positive): “Glycoforms were categorized in Oligo (Oligomannose), Hybrid, and Complex as well as subtypes in Complex, described in the previous study (Watanabe et al., 2020).”
• SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2 (2020, background): “Recombinant ectodomains migrate as a trimer assuming a monomer molecular mass of ~142,000 and 22 N-linked glycans per monomer (Watanabe et al., 2020).”
• Molecular Architecture of the SARS-CoV-2 Virus (2020, positive): “Furthermore, the lower levels of oligomannose-type glycans compared to HIV and LASV are also consistent with lower glycan density (Watanabe et al., 2020b; Watanabe et al., 2018).”
• The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity (2020, neutral): “As N165 and N234 are located near the RBD region (Watanabe et al., 2020), these mutants may affect some epitopes targeted by neutralizing mAbs.”
• ScanNet: an interpretable geometric deep learning model for structure-based protein binding site prediction (2021, background): “Finally, the network predicted with high confidence one previously unreported conformational epitope constituted by three fragments in the vicinity of the glycosylated [55] Asn 657.”