Evidence map›Paper›PMID 33103998›Full record

ArticleeLife2020

Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration.

Qi Yang, Thomas A Hughes, Anju Kelkar, Xinheng Yu, Kai Cheng, Sheldon Park, Wei-Chiao Huang, Jonathan F Lovell, Sriram Neelamegham

Open access · goldAbstract read
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.

0numbers the graph read from it
0cells of the map it votes in
142citing papers in PubMed
4.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

142 citing papers in PubMed, 226 citations in OpenAlex.

  1. Iterative Bump-and-Hole Engineering Creates a Bioorthogonal Reporter forJournal of the American Chemical Society · 2026
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  4. Iterative Bump-and-hole engineering creates a bioorthogonal reporter forbioRxiv : the preprint server for biology · 2026
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  7. Review
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  11. The Role of Glycans in Human Immunity-A Sweet Code.Molecules (Basel, Switzerland) · 2025
    Review
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  13. Article
  14. Review
  15. Article
  16. Article
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  19. Review
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82 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Qi Yang *Chemical & Biological Engineering, State University of New York, Buffalo, United States.ORCID 0000-0003-4308-4382
Thomas A Hughes *Chemical & Biological Engineering, State University of New York, Buffalo, United States.ORCID 0000-0002-7887-6876
Anju Kelkar *Chemical & Biological Engineering, State University of New York, Buffalo, United States.
Xinheng YuChemical & Biological Engineering, State University of New York, Buffalo, United States.
Kai ChengChemical & Biological Engineering, State University of New York, Buffalo, United States.
Sheldon ParkChemical & Biological Engineering, State University of New York, Buffalo, United States.
Wei-Chiao HuangBiomedical Engineering, State University of New York, Buffalo, United States.
Jonathan F LovellChemical & Biological Engineering, State University of New York, Buffalo, United States.ORCID 0000-0002-9052-884X
Sriram NeelameghamChemical & Biological Engineering, State University of New York, Buffalo, United States.ORCID 0000-0002-1371-8500
University at Buffalo, State University of New York · US

Funding

Systems Biology of GlycosylationR01HL103411 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI NEELAMEGHAM, SRIRAM · 2011 to 2025
$7.1M
Synthetic glycan biomarkers: Novel reporters of cell metabolismR21GM126537 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI NEELAMEGHAM, SRIRAM · 2018 to 2019
$439k
High content glycomics analysis using next generation sequencing technologyR21GM133195 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI NEELAMEGHAM, SRIRAM · 2019 to 2020
$436k
Engineering of glycosyltransferases to obtain glycan binding proteinsR21GM139160 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI NEELAMEGHAM, SRIRAM, PARK, SHELDON · 2020 to 2021
$422k
NHLBI NIH HHS R01 HL103411NIGMS NIH HHS R21 GM126537NIGMS NIH HHS R21 GM133195NIGMS NIH HHS R21 GM139160NIH HHS GM126537NIH HHS GM133195NIH HHS GM139160NIH HHS HL103411
6 · The paper itself

Abstract

The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated. The impact of this post-translational modification on viral entry is yet unestablished. We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus. We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding. However, these carbohydrates played a major role in regulating viral entry. Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells. Blocking O-glycan elaboration also partially blocked viral entry. Mechanistic studies suggest multiple roles for glycans during viral entry. Among them, inhibition of N-glycan biosynthesis enhanced Spike-protein proteolysis. This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry. Overall, chemical inhibitors of glycosylation may be evaluated for COVID-19.

Indexed as

AlkaloidsAngiotensin-Converting Enzyme 2Gene Knockout TechniquesGlycosylationHEK293 CellsHost Microbial InteractionsHumansMass SpectrometryMolecular Dynamics SimulationPolysaccharidesProtein BindingProtein Processing, Post-TranslationalReceptors, VirusSARS-CoV-2Spike Glycoprotein, CoronavirusVirus InternalizationACE2 protein, humanAlkaloidsAngiotensin-Converting Enzyme 2kifunensinePolysaccharidesReceptors, VirusSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2biochemistrychemical biologyCOVID-19furinglycosciencehumaninfectious diseasekifunensinemicrobiologySARS-CoV-2spikevirus

Identifiers

PMID33103998
PMCPMC7685702
OpenAlexW3094617920

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.