The emergence of the betacoronavirus, SARS-CoV-2, the causative agent of COVID-19, represents a significant 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. 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 glycanprocessing 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.

Glycosylation is a ubiquitous post-translational modification responsible for a multitude of crucial biological roles. As obligate parasites, viruses exploit host-cell machinery to glycosylate their own proteins during replication. Viral envelope proteins from a variety of human pathogens including HIV-1, influenza virus, Lassa virus, SARS, Zika virus, dengue virus, and Ebola virus have evolved to be extensively glycosylated. These host-cell derived glycans facilitate diverse structural and functional roles during the viral life-cycle, ranging from immune evasion by glycan shielding to enhancement of immune cell infection. In this review, we highlight the imperative and auxiliary roles glycans play, and how specific oligosaccharide structures facilitate these functions during viral pathogenesis. We discuss the growing efforts to exploit viral glycobiology in the development of anti-viral vaccines and therapies.