Evidence map›Paper›PMID 36243815›Full record

ArticleNature communications2022

Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways.

Naoko Iwata-Yoshikawa, Masatoshi Kakizaki, Nozomi Shiwa-Sudo, Takashi Okura, Maino Tahara, Shuetsu Fukushi, Ken Maeda, Miyuki Kawase, Hideki Asanuma, Yuriko Tomita and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
10.3field-weighted citation impact, top 1% 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

66 citing papers in PubMed, 106 citations in OpenAlex.

  1. Intelligent Programmable Membrane Nanosponge for Early Virus Blocking.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  6. TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026
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  9. Review
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  15. An orally available MNature communications · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

6 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

16 authors at 1 institution in 1 country.

Naoko Iwata-Yoshikawa *Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
Masatoshi Kakizaki *Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
Nozomi Shiwa-SudoDepartment of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
Takashi OkuraDepartment of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
Maino TaharaDepartment of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
Shuetsu FukushiDepartment of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
Ken MaedaDepartment of Veterinary Science, National Institute of Infectious Diseases, Tokyo, Japan.
Miyuki KawaseDepartment of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
Hideki AsanumaCenter for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Tokyo, Japan.
Yuriko TomitaCenter for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Tokyo, Japan.
Ikuyo TakayamaCenter for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Tokyo, Japan.
Shutoku MatsuyamaCenter for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Tokyo, Japan.
Kazuya ShiratoDepartment of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
Tadaki SuzukiDepartment of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
Noriyo NagataDepartment of Pathology, National Institute of Infectious Diseases, Tokyo, Japan. nnagata@niid.go.jp.ORCID 0000-0001-9147-1438
Makoto TakedaDepartment of Virology III, National Institute of Infectious Diseases, Tokyo, Japan. mtakeda@m.u-tokyo.ac.jp.ORCID 0000-0002-8194-7727
National Institute of Infectious Diseases · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In cultured cells, SARS-CoV-2 infects cells via multiple pathways using different host proteases. Recent studies have shown that the furin and TMPRSS2 (furin/TMPRSS2)-dependent pathway plays a minor role in infection of the Omicron variant. Here, we confirm that Omicron uses the furin/TMPRSS2-dependent pathway inefficiently and enters cells mainly using the cathepsin-dependent endocytosis pathway in TMPRSS2-expressing VeroE6/TMPRSS2 and Calu-3 cells. This is the case despite efficient cleavage of the spike protein of Omicron. However, in the airways of TMPRSS2-knockout mice, Omicron infection is significantly reduced. We furthermore show that propagation of the mouse-adapted SARS-CoV-2 QHmusX strain and human clinical isolates of Beta and Gamma is reduced in TMPRSS2-knockout mice. Therefore, the Omicron variant isn't an exception in using TMPRSS2 in vivo, and analysis with TMPRSS2-knockout mice is important when evaluating SARS-CoV-2 variants. In conclusion, this study shows that TMPRSS2 is critically important for SARS-CoV-2 infection of murine airways, including the Omicron variant.

Indexed as

COVID-19SARS-CoV-2AnimalsCathepsinsFurinHumansMiceMice, KnockoutPeptide HydrolasesSerine EndopeptidasesSpike Glycoprotein, CoronavirusVirus InternalizationCathepsinsFurinPeptide HydrolasesSerine EndopeptidasesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2TMPRSS2 protein, humanTMPRSS2 protein, mouse

Identifiers

PMID36243815
PMCPMC9568946
OpenAlexW4306290643

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.