Variations in O-Glycosylation Patterns Influence Viral Pathogenicity, Infectivity, and Transmissibility in SARS-CoV-2 Variants

Abstract

The highly glycosylated S protein plays a vital role in host cell invasion, making it the principal target for vaccine development. Differences in mutations observed on the spike (S) protein of SARS-CoV-2 variants may result in distinct glycosylation patterns, thus influencing immunological evasion, infectivity, and transmissibility. The glycans can mask key epitopes on the S1 protein and alter its structural conformation, allowing the virus to escape the immune system. Therefore, we comprehensively characterize O-glycosylation in eleven variants of SARS-CoV-2 S1 subunits to understand the differences observed in the biology of the variants. In-depth characterization was performed with a double digestion strategy and an efficient LC-MS/MS approach. We observed that O-glycosylation is highly conserved across all variants in the region between the NTD and RBD, whereas other domains and regions exhibit variation in O-glycosylation. Notably, omicron has the highest number of O-glycosylation sites on the S1 subunit. Also, omicron has the highest level of sialylation in the RBD and RBM functional motifs. Our findings may shed light on how differences in O-glycosylation impact viral pathogenicity in variants of SARS-CoV-2 and facilitate the development of a robust vaccine with high protective efficacy against the variants of concern.

Multi Omics Applications in Biological Systems

“…These branches of omics science delve into understanding the structure, function, and dynamics of glycans attached to proteins and lipids across different biological systems and their role in health and disease. By analyzing these structures, glycomics and glycoproteomics analysis provides insights into cellular communication [ 69 , 70 ], immune response [ 71 ], pathogen interaction [ 72 , 73 ], and disease progression [ 74 ], making it a crucial field in biomedical research and therapeutic development. Advanced technologies such as high-performance liquid chromatography–mass spectrometry (LC-MS) are employed to decipher the complex and diverse structures of glycans and the protein O - and N -site heterogeneity.…”

“…The glycopeptides can also be derivatized, targeting the peptide N -terminus using tandem mass tags (TMTs) [ 82 ]. Alterations in glycan expression are linked to various diseases, including cancer [ 83 , 84 , 85 ], neurodegenerative diseases [ 86 , 87 , 88 ], autoimmune disorders [ 89 , 90 ], and infectious diseases [ 73 , 91 , 92 ]. These changes can impact cell signaling [ 93 ], immune recognition [ 94 ], and molecular stability [ 95 ], leading to altered cellular behaviors and disease progression.…”

Metabolomic Changes in Rat Serum after Chronic Exposure to Glyphosate-Based Herbicide

“…Omics is an emerging field that holds promise to shine light on the molecular mechanisms causing diseases [ 10 ]. Most recently, proteomics, glycomics, glycoproteomics, and metabolomics changes have been implicated in several diseases [ 11 , 12 , 13 , 14 , 15 , 16 ]. To facilitate better understanding of diseases, many omics fields have advanced methods for better identification of glycans, glycopeptides, and their isomers [ 17 , 18 , 19 , 20 ], and have developed several bioinformatic tools [ 21 ] that improve interpretations of omics data.…”