Evidence map›Paper›PMID 33578036›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021

Nanoluciferase complementation-based bioreporter reveals the importance of N-linked glycosylation of SARS-CoV-2 S for viral entry.

Taha Azad, Ragunath Singaravelu, Zaid Taha, Taylor R Jamieson, Stephen Boulton, Mathieu J F Crupi, Nikolas T Martin, Emily E F Fekete, Joanna Poutou, Mina Ghahremani and 14 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.6field-weighted citation impact, top 14% 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

19 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022
    Review
  6. Identification of FDA-approved bifonazole as a SARS-CoV-2 blocking agent following a bioreporter drug screen.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Glycosylation of SARS-CoV-2: structural and functional insights.Analytical and bioanalytical chemistry · 2021
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Impact of SpecificFrontiers in plant science · 2021
    Article
  19. Article
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

24 authors at 5 institutions in 1 country.

Taha AzadCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Ragunath SingaraveluCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Zaid TahaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Taylor R JamiesonCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Stephen BoultonCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Mathieu J F CrupiCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Nikolas T MartinCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Emily E F FeketeCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Joanna PoutouCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Mina GhahremaniDepartment of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
Adrian PelinCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Kazem NouriPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Reza RezaeiCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Christopher Boyd MarshallPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Masahiro EnomotoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Rozanne ArulanandamCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Nouf AlluqmaniCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Reuben SamsonLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Anne-Claude GingrasLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
D William CameronCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Peter A GreerDepartment of Pathology and Molecular Medicine, Queens University, Kingston, ON K7L 3N6, Canada.
Carolina S IlkowCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Jean-Simon DialloCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
John C BellCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada. Electronic address: jbell@ohri.ca.
University of Ottawa · CAUniversity Health Network · CAUniversity of Toronto · CAOttawa Hospital · CAQueen's University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ongoing COVID-19 pandemic has highlighted the immediate need for the development of antiviral therapeutics targeting different stages of the SARS-CoV-2 life cycle. We developed a bioluminescence-based bioreporter to interrogate the interaction between the SARS-CoV-2 viral spike (S) protein and its host entry receptor, angiotensin-converting enzyme 2 (ACE2). The bioreporter assay is based on a nanoluciferase complementation reporter, composed of two subunits, large BiT and small BiT, fused to the S receptor-binding domain (RBD) of the SARS-CoV-2 S protein and ACE2 ectodomain, respectively. Using this bioreporter, we uncovered critical host and viral determinants of the interaction, including a role for glycosylation of asparagine residues within the RBD in mediating successful viral entry. We also demonstrate the importance of N-linked glycosylation to the RBD's antigenicity and immunogenicity. Our study demonstrates the versatility of our bioreporter in mapping key residues mediating viral entry as well as screening inhibitors of the ACE2-RBD interaction. Our findings point toward targeting RBD glycosylation for therapeutic and vaccine strategies against SARS-CoV-2.

Indexed as

Biological AssayAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAsparagineBinding SitesCOVID-19COVID-19 Drug TreatmentGenes, ReporterGlycosylationHEK293 CellsHost-Pathogen InteractionsHumansLectinsLuciferasesLuminescent MeasurementsProtein BindingACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAsparagineLectinsLuciferasesReceptors, VirusSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-22019-nCoVbioluminescencebioreportercoronavirusCOVID-19high-throughput screeningSARS-CoV-2viral entry

Identifiers

PMID33578036
PMCPMC7872859
OpenAlexW3126740860

What OpenQuestion holds

Textmetadata
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.