Evolving spike-proteinN-glycosylation in SARS-CoV-2 variants

Abstract

AbstractSince >3 years, SARS-CoV-2 has plunged humans into a colossal pandemic. Henceforth, multiple waves of infection have swept through the human population, led by variants that were able to partially evade 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 heavilyN-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 host-installedN-glycans. Using highly-sensitive DeGlyPHER approach, we compared theN-glycan landscape on spikes of the SARS-CoV-2 Wuhan-Hu-1 strain to seven WHO-defined variants of concern/interest, using recombinantly expressed, soluble spike-protein trimers, sharing same stabilizing-mutations. We found thatN-glycan processing is conserved at most sites. However, in multiple variants, processing ofN-glycans from high mannose- to complex-type is reduced at sites N165, N343 and N616, implicated in spike-protein function.