Evolving spike-protein N-glycosylation in SARS-CoV-2 variants

Abstract

It has been three years since SARS-CoV-2 emerged and the world plunged into a “once in a century” pandemic. Since then, multiple waves of infection have swept through the human population, led by variants that were able to evade any acquired immunity. The co-evolution of SARS-CoV-2 variants with human immunity provides an excellent opportunity to study the interaction between viral pathogens and their human hosts. The heavily N-glycosylated spike-protein of SARS-CoV-2 plays a pivotal role in initiating infection and is the target for host immune response, both of which are impacted by hostinstalled N-glycans. We compared the N-glycan landscape of recombinantly expressed, stabilized, soluble spike-protein trimers representing seven of the most prominent SARS-CoV-2 variants and found that N-glycan processing is conserved at most sites. However, in multiple variants, processing of Nglycans from high mannose- to complex-type is reduced at sites N165, N343 and N616, implicated in spike-protein function.