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SARS-CoV-2 proteins

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    N-glycosylation network construction and analysis to modify glycans on the spike S glycoprotein PROTEIN of SARS-CoV-2.

    Authors: Sridevi Krishnan; Giri P Krishnan

    doi:10.1101/2020.06.23.167791 Date: 2020-06-24 Source: bioRxiv

    Background The spike S-protein PROTEIN S-protein HGNC of SARS-CoV-2 is N-glycosylated. The N-glycan structure and composition of this glycoprotein influence how the virus interacts with host cells.Objective To identify a putative N-glycan biosynthesis pathway of SARS-CoV-2 (HEK293 cell recombinant) from previously published mass spectrometric studies, and to identify what effect blocking some enzymes has on the overall glycoprotein profile. Finally, our goal was to provide the biosynthesis network, and glycans in easy-to-use format for further glycoinformatics work.Methods We reconstructed the glycosylation network based on previously published empirical data using GNAT HGNC, a glycosylation network analysis tool. Our compilation of the network tool had 23 glycosyltransferase and glucosidase enzymes, and could infer the pathway of glycosylation machinery based on glycans identified in the virus spike protein PROTEIN. Once the glycan biosynthesis pathway was generated, we simulated the effect of blocking specific enzymes - Mannosidase-II and alpha-1,6-fucosyltransferase HGNC to see how they would affect the biosynthesis network.Results Of the 23 enzymes, a total of 12 were involved in glycosylation of SARS-CoV-2 - Man-Ia, MGAT1 HGNC, MGAT2 HGNC, MGAT4, MGAT5 HGNC, B4GalT HGNC, B4GalT HGNC, Man II HGNC, SiaT, ST3GalI HGNC, ST3GalVI HGNC and FucT8. Blocking enzymes resulted in a substantially modified glycan profile of the protein.Conclusions A network analysis of N-glycan biosynthesis of SARS-CoV-2 spike PROTEIN SARS-CoV-2 spike MESHD protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies. Variations in the final N-glycan profile of the virus, given its site-specific microheterogeneity, could be a factor in the host response to the infection and response to antibodies. Here we provide all the resources generated - the glycans derived from mass spectrometry and intermediate glycans in glycoCT xml format, and the biosynthesis network for future drug and vaccine development work.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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MeSH Disease
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SARS-CoV-2 Proteins


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