Transcriptomic Analysis of Respiratory Tissue and Cell Line Models to Examine Glycosylation Machinery during SARS-CoV-2 Infection

Abstract

Glycosylation, being the most abundant post-translational modification, plays a profound role affecting expression, localization and function of proteins and macromolecules in immune response to infection. Presented are the findings of a transcriptomic analysis performed using high-throughput functional genomics data from public repository to examine the altered transcription of the human glycosylation machinery in response to SARS-CoV-2 stimulus and infection. In addition to the conventional in silico functional enrichment analysis methods we also present results from the manual analysis of biomedical literature databases to bring about the biological significance of glycans and glycan-binding proteins in modulating the host immune response during SARS-CoV-2 infection. Our analysis revealed key immunomodulatory lectins, proteoglycans and glycan epitopes implicated in exerting both negative and positive downstream inflammatory signaling pathways, in addition to its vital role as adhesion receptors for SARS-CoV-2 pathogen. A hypothetical correlation of the differentially expressed human glycogenes with the altered host inflammatory response and the cytokine storm-generated in response to SARS-CoV-2 pathogen is proposed. These markers can provide novel insights into the diverse roles and functioning of glycosylation pathways modulated by SARS-CoV-2, provide avenues of stratification, treatment, and targeted approaches for COVID-19 immunity and other viral infectious agents.

Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic

“…Detecting changes in gene expression in relevant tissues during SARS-CoV-2 infection through various functional genomic methods (e.g., microarrays and RNA-sequencing-based transcriptomics) can increase understanding of molecular mechanisms involved in COVID-19, plus host-pathogen interactions (8)(9)(10). Transcriptomic studies in COVID-19 patients used lung epithelial cells, nasopharyngeal swabs, bronchoalveolar lavage fluid (9,(11)(12)(13)(14), or peripheral blood mononuclear cells (PBMCs) (6,8,15). However, differential gene expression analysis focuses more on individual effects of genes (16), whereas genes interact in complex biological gene networks (17).…”

Three-Dimensional Visualization of Viral Structure, Entry, and Replication Underlying the Spread of SARS-CoV-2

“…Complementary structural and mass spectrometry analyses of the SARS-CoV-2 S protein confirmed that, like the related proteins from SARS-CoV and MERS-CoV viruses, the SARS-CoV-2 S protein is also extensively glycosylated. , Glycosylation has a myriad of roles in viral pathobiology including shielding vulnerable neutralizing epitopes, shaping viral tropism, and mediating S protein folding and stability. − Figure A shows that there are 22, 22, and 23 glycosylation sites in the SARS-CoV-2, SARS-CoV, and MERS-CoV S proteins, respectively, with glycosylation preferentially localizing to the NTD, S1/S2 boundary, and stem helix of the S2 fusion domain. , Using the first reported structure of the SARS-CoV-2 spike protein (6VSB), Grant et al generated 3D structures of the S protein glycoforms and subjected them to molecular dynamic (MD) simulations to determine the antibody-accessible surface area . Despite only accounting for 17% of the molecular weight of the S trimer, Grant et al found that the glycans shield approximately 40% of the S protein surface (Figure B).…”

“… 94 , 95 Glycosylation has a myriad of roles in viral pathobiology including shielding vulnerable neutralizing epitopes, shaping viral tropism, and mediating S protein folding and stability. 94 − 100 Figure 10 A shows that there are 22, 22, and 23 glycosylation sites in the SARS-CoV-2, SARS-CoV, and MERS-CoV S proteins, respectively, with glycosylation preferentially localizing to the NTD, S1/S2 boundary, and stem helix of the S2 fusion domain. 94 , 95 Using the first reported structure of the SARS-CoV-2 spike protein ( 6VSB ), Grant et al generated 3D structures of the S protein glycoforms and subjected them to molecular dynamic (MD) simulations to determine the antibody-accessible surface area.…”

Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice

“…The Spike protein and, more specifically, its receptor-binding domain (RBD) on the virus surface are responsible for binding to human angiotensin-converting enzyme 2 (hACE2) on the host cell. Hence, because of their central role in viral entry, the Spike and the RBD are established immunogens in SARS-CoV-2 vaccines ( 2 , 3 ). mRNA-based and viral-vectored vaccines encoding the Spike protein have gained regulatory approvals and are being massively deployed presently.…”