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bioRxiv · 10.1101/2023.05.08.539897

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

Baboo, S.·Diedrich, J. K.·Torres, J. L.·Copps, J.·Singh, B.·Garrett, P. T.·Ward, A. B.·Paulson, J. C.·Yates, J. R.
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Abstract

Since >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 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 host-installed N-glycans. Using highly-sensitive DeGlyPHER approach, we compared the N-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 that N-glycan processing is conserved at most sites. However, in multiple variants, processing of N-glycans from high mannose- to complex-type is reduced at sites N165, N343 and N616, implicated in spike-protein function.

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Baboo, S., Diedrich, J. K., Torres, J. L., Copps, J., Singh, B., Garrett, P. T., Ward, A. B., Paulson, J. C., Yates, J. R.. 2023-05-09. Evolving spike-protein N-glycosylation in SARS-CoV-2 variants. https://doi.org/10.1101/2023.05.08.539897

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