Direct Comparison of N-Glycans and Their Isomers Derived from Spike Glycoprotein 1 of MERS-CoV, SARS-CoV-1, and SARS-CoV-2

Abstract

The emergence of COVID-19 pandemic has engaged the scientific community around the globe in the rapid development of effective therapeutics and vaccines. Owing to its crucial role in the invasion of the host cell, spike (S) glycoprotein is one of the major targets in these studies. The S1 subunit of the S protein (S1 protein) accommodates the receptor-binding domain, which enables the initial binding of the virus to the host cell. Being a heavily glycosylated protein, numerous studies have investigated its glycan composition. However, none of the studies have explored the isomeric glycan distribution of this protein. Furthermore, this isomeric glycan distribution has never been compared to that in S1 proteins of other coronaviruses, severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome coronavirus, which were responsible for past epidemics. This study explores the uncharted territory of the isomeric glycan distribution in the coronaviruses’ S1 protein using liquid chromatography coupled to tandem mass spectrometry. We believe that our data would facilitate future investigations to study the role of isomeric glycans in coronavirus viral pathogenesis.

Site‐specific glycosylation of SARS‐CoV‐2: Big challenges in mass spectrometry analysis

“…Different sources of the S protein, expression systems, and proteases used for sample digestion are also shown for comparison reports used pGlyco [58], and a few researchers used proprietary software. Interestingly, several reports classified glycans into numerous subgroups such us complex/hybrid and oligomannose without glycan structure-based separation using chromatographic techniques [87] or ion mobility [83].…”

Binding of synthetic carbohydrate receptors to enveloped virus glycans: Insights from molecular dynamics simulations

“…The monosaccharides are coded according to the SNFG notation [ 35 ]. (C) 33 studied N -glycans common to EnV [ [32] , [33] , [34] ], divided into three major types. The complex N -glycan are divided into four subgroups, depending on the type of a carbohydrate at the non-reducing end.…”

“…As for the binding targets, we selected 33 N -glycans common to the surfaces of flavi- and coronaviruses [ [31] , [32] , [33] , [34] ]. These N -glycans possess conserved structural features that were used to sort them into three groups ( Fig.…”

“…Fine-tuning the specificity of the SCRs towards selected EnV glycans would (1) improve the inhibition of the viral docking to the host receptor, thus reducing the chance of the infection, and (2) decrease the likelihood of off-site toxicity caused by binding to the host N -glycans. In this study, we report detailed molecular dynamics (MD) simulations analysis of the binding between 10 tetrapodal SCRs and 33 N -glycans common to surfaces of ZIKV [ 31 ], MERS-CoV, SARS-CoV, and SARS-CoV-2 [ [32] , [33] , [34] ]. These simulations capture how small modifications in N -glycan or SCR structures alter the binding geometries and association strengths, and provide a molecular-level rationale for the differences in the observed antiviral activity of the SCRs, which can guide the design of the next generation of EnV glycan binding-receptors.…”

“Multiomics” Approaches to Understand and Treat COVID-19: Mass Spectrometry and Next-Generation Sequencing

“…Techniques based on mass spectrometry have been critical for understanding the glycosylation of SARS-CoV-2 spike protein [27,[101][102][103][104][105][106]. Glycosylation of the spike protein of coronavirus and other viral proteins are crucial to the infection process because the modification shields immunogenic epitopes, and impact immunological pressure across the protein surface [107,108].…”