Evidence map›Paper›PMID 35963244›Full record

ArticleCell reports2022

SARS-CoV-2 spike N-terminal domain modulates TMPRSS2-dependent viral entry and fusogenicity.

Bo Meng, Rawlings Datir, Jinwook Choi, CITIID-NIHR Bioresource COVID-19 Collaboration, John R Bradley, Kenneth G C Smith, Joo Hyeon Lee, Ravindra K Gupta

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 3% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. PotentJournal of virology · 2026
    Article
  6. Clade C MERS-CoV camel strains vary in protease utilization during viral entry.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. The accomplices: Heparan sulfates and N-glycans foster SARS-CoV-2 spike:ACE2 receptor binding and virus priming.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. SARS-CoV-2 biology and host interactions.Nature reviews. Microbiology · 2024
    Review
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

8 authors at 3 institutions in 2 countries.

Bo MengCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK. Electronic address: bm432@cam.ac.uk.
Rawlings DatirCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK.
Jinwook ChoiWellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK.
CITIID-NIHR Bioresource COVID-19 Collaboration
John R BradleyDepartment of Medicine, University of Cambridge, Cambridge, UK; NIHR Bioresource, Cambridge, UK.
Kenneth G C SmithCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK.
Joo Hyeon LeeWellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
Ravindra K GuptaCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK; Africa Health Research Institute, Durban, South Africa. Electronic address: rkg20@cam.ac.uk.
University of Cambridge · GBWellcome/MRC Cambridge Stem Cell Institute · GBAfrica Health Research Institute · ZA

Funding

Medical Research Council MC_PC_17230Medical Research Council MR/W005611/1Wellcome TrustWellcome Trust WT108082AIA
6 · The paper itself

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike N-terminal domain (NTD) remains poorly characterized despite enrichment of mutations in this region across variants of concern (VOCs). Here, we examine the contribution of the NTD to infection and cell-cell fusion by constructing chimeric spikes bearing B.1.617 lineage (Delta and Kappa variants) NTDs and generating spike pseudotyped lentivirus. We find that the Delta NTD on a Kappa or wild-type (WT) background increases S1/S2 cleavage efficiency and virus entry, specifically in lung cells and airway organoids, through use of TMPRSS2. Delta exhibits increased cell-cell fusogenicity that could be conferred to WT and Kappa spikes by Delta NTD transfer. However, chimeras of Omicron BA.1 and BA.2 spikes with a Delta NTD do not show more efficient TMPRSS2 use or fusogenicity. We conclude that the NTD allosterically modulates S1/S2 cleavage and spike-mediated functions in a spike context-dependent manner, and allosteric interactions may be lost when combining regions from more distantly related VOCs.

Indexed as

COVID-19Virus InternalizationHumansSARS-CoV-2Serine EndopeptidasesSpike Glycoprotein, CoronavirusSerine EndopeptidasesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2TMPRSS2 protein, humanCP: MicrobiologyDeltaentryfusogenicityNTDOmicronOrganoidSARS-CoV-2spikeTMPRSS2

Identifiers

PMID35963244
PMCPMC9346021
OpenAlexW4289528710

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.