Evidence map›Paper›PMID 36048924›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

SARS-CoV-2 requires acidic pH to infect cells.

Alex J B Kreutzberger, Anwesha Sanyal, Anand Saminathan, Louis-Marie Bloyet, Spencer Stumpf, Zhuoming Liu, Ravi Ojha, Markku T Patjas, Ahmed Geneid, Gustavo Scanavachi and 11 more

Expression of concernAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 64 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

64 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Transcriptional Analysis ofInternational journal of molecular sciences · 2025
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Alex J B KreutzbergerDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115.
Anwesha SanyalDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115.
Anand SaminathanDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115.
Louis-Marie BloyetDepartment of Molecular Microbiology, Washington University in Saint Louis, St. Louis, MO 63110.ORCID 0000-0002-5648-3190
Spencer StumpfDepartment of Molecular Microbiology, Washington University in Saint Louis, St. Louis, MO 63110.
Zhuoming LiuDepartment of Molecular Microbiology, Washington University in Saint Louis, St. Louis, MO 63110.ORCID 0000-0001-8198-0976
Ravi OjhaDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, 00290 Finland.
Markku T PatjasDepartment of Otorhinolaryngology and Phoniatrics - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, 00290 Finland.ORCID 0000-0001-7346-2554
Ahmed GeneidDepartment of Otorhinolaryngology and Phoniatrics - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, 00290 Finland.
Gustavo ScanavachiDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115.
Catherine A DoyleDepartment of Pharmacology, University of Virginia, Charlottesville, VA 22903.
Elliott SomervilleProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
Ricardo Bango Da Cunha CorreiaDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115.
Giuseppe Di CaprioProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
Sanna Toppila-SalmiDepartment of Allergy, University of Helsinki and Helsinki University Hospital, Helsinki, 00290 Finland.
Antti MäkitieDepartment of Otorhinolaryngology and Phoniatrics - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, 00290 Finland.
Volker KiesslingCenter for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA 22903.ORCID 0000-0002-9388-5703
Olli VapalahtiDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, 00290 Finland.ORCID 0000-0003-2270-6824
Sean P J WhelanDepartment of Molecular Microbiology, Washington University in Saint Louis, St. Louis, MO 63110.ORCID 0000-0003-1564-8590
Giuseppe BalistreriDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, 00290 Finland.ORCID 0000-0002-3585-559X
Tom KirchhausenDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115.

Funding

MOLECULAR BASIS OF VIRAL INFECTIVITYT32AI007245 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Aaron Gregory Schmidt · 1985 to 2026
$11.3M
VIRAL SPIKE GLYCOPROTEIN-MEDIATED MEMBRANE POTENTIALR01AI030557 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI TAMM, LUKAS K · 1991 to 2022
$6.2M
VISUALIZATION OF SUBCELLULAR DYNAMICS IN MULTICELLULAR ORGANISMSR35GM130386 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI TOMAS KIRCHHAUSEN · 2019 to 2026
$4.0M
Mechanism and Inhibition of SARS-CoV-2 EntryR01AI163019 · NIAID · WASHINGTON UNIVERSITY · PI KIRCHHAUSEN, TOMAS, WHELAN, SEAN PJ · 2021 to 2025
$3.8M
MOLECULAR MECHANISMS OF VIRAL MEMBRANE FUSIONR37AI030557 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI TAMM, LUKAS K · 2003 to 2011
$3.4M
NIAID NIH HHS R01 AI030557NIAID NIH HHS R01 AI163019NIAID NIH HHS R37 AI030557NIAID NIH HHS T32 AI007245NIGMS NIH HHS R35 GM130386
6 · The paper itself

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry starts with membrane attachment and ends with spike (S) protein-catalyzed membrane fusion depending on two cleavage steps, namely, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time three-dimensional single-virion tracking, we show that fusion and genome penetration require virion exposure to an acidic milieu of pH 6.2 to 6.8, even when furin and TMPRSS2 cleavages have occurred. We detect the sequential steps of S1-fragment dissociation, fusion, and content release from the cell surface in TMPRRS2-overexpressing cells only when exposed to acidic pH. We define a key role of an acidic environment for successful infection, found in endosomal compartments and at the surface of TMPRSS2-expressing cells in the acidic milieu of the nasal cavity.

Indexed as

COVID-19Nasal CavitySARS-CoV-2Serine EndopeptidasesVirus InternalizationFurinHumansHydrogen-Ion ConcentrationSpike Glycoprotein, CoronavirusFurinSerine EndopeptidasesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2TMPRSS2 protein, human3D imaginginfection routelive-cell imagingSARS-CoV-2virus entry

Identifiers

PMID36048924
PMCPMC9499588

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.