SARS-CoV-2 variants show altered glycan processing COVID19 pandemic variants immunity viralpathogens spikeprotein Nglycans research hostinteraction virology biorxivpreprint scrippsresearch
By Dr. Chinta SidharthanMay 15 2023Reviewed by Benedette Cuffari, M.Sc. In a recent study posted to the bioRxiv* preprint server, researchers at the Scripps Research Institute examine stabilized, recombinantly expressed, soluble spike-protein trimers from the seven most prominent severe respiratory syndrome coronavirus 2 variants to compare the N -glycan landscape and understand the interactions between the virus and host cell.
Background The coronavirus disease 2019 , which originated in late 2019 in Wuhan, China, has claimed over 6.9 million lives worldwide. SARS-CoV-2 has rapidly evolved since the onset of the pandemic and acquired various novel mutations that have increased its transmissibility among humans. The ancestral SARS-CoV-2 strain Wuhan-Hu-1 was dominant during 2020 and then evolved to produce five major variants of concern , including the Alpha, Beta, Gamma, Delta, and Omicron variants.
About the study In the present study, researchers evaluate the N-glycan landscape of the Wuhan-Hu-1 SARS-CoV-2 spike protein, as well as the SARS-CoV-2 variants Alpha, Beta, Mu, Gamma, Delta, Lambda, and Omicron spike proteins. The N-glycan landscape was also compared with that of a recombinant spike protein that has been recently authorized by the United States Food and Drug Administration for emergency use as a vaccine.
Results The N-glycan processing sites in the spike protein were conserved across most of the SARS-CoV-2 variants. The head of the spike protein comprised over 1,100 amino acids and contained eight N-glycosylation sites in the N-terminal domain, two N-glycosylation sites in the RBD, and additional nine N-glycosylation sites. Comparatively, the stalk of the spike protein, with each protomer comprising less than 150 amino acids, contained three N-glycosylation sites.
The difference between the results of the hierarchical clustering and evolutionary patterns deciphered from analyzing the nucleic acid mutations also suggested that glycan changes were under a selection pressure that was more dependent on a higher-order structure than the primary protein sequence. Respiratory tract cells expressed very low levels of ACE-2 receptors but were the most affected by the Delta variant. Thus, the mannose-binding receptors and low glycan processing in the three sites for the high pathogenicity of the Delta variant, however, need to be further examined.