Vulnerabilities in Coronavirus Glycan Shields Despite Extensive Glycosylation

May 27, 2020

Publication type

Journal Article


Nature Communications

Volume and Number



Watanabe Y, Berndsen ZT, Raghwani J, Seabright GE, Allen JD, Pybus OG, McLellan JS, Wilson IA, Bowden TA, Ward AB, Crispin M


Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential. Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein. Coronavirus S proteins are extensively glycosylated, encoding around 66-87 N-linked glycosylation sites per trimeric spike.

Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs. We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.

Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.


  • We initially sought to quantitatively assess the composition of the carbohydrate structures displayed on the S glycoproteins.
  • Observation of both complex and oligomannose-type glycans reveals that the majority of N-linked glycans can be processed, although there is limited processing at specific sites across the S proteins.
  • It is also interesting to note that the distribution of oligomannose-type glycans was broad, with Man5GlcNAc2 to Man9GlcNAc2 glycans all present, without one particular dominant peak, as is the case for some viral glycoproteins, such as HIV-1 Env.
  • The proportion of oligomannose-type glycans on recombinant coronavirus S proteins is consistent with previous studies performed on virally derived MERS and SARS coronavirus S proteins.
  • Coronaviruses have been previously been reported to form virions by budding into the lumen of endoplasmic reticulum-Golgi intermediate compartments (ERGIC).
  • Observations of hybrid and complex-type glycans on virally derived material would suggest that it is likely that coronavirus virions travel through the Golgi apparatus after virion formation in the ERGIC en route to the cell surface, thus supporting recombinant immunogens as models of viral glycoproteins.