Evidence map›Paper›PMID 35110354›Full record

ArticleLife science alliance2022

Topical TMPRSS2 inhibition prevents SARS-CoV-2 infection in differentiated human airway cultures.

Wenrui Guo, Linsey M Porter, Thomas Wm Crozier, Matthew Coates, Akhilesh Jha, Mikel McKie, James A Nathan, Paul J Lehner, Edward Jd Greenwood, Frank McCaughan

Open access · goldAbstract read
In one paragraph

Article in Life science alliance, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. One Week of Oral Camostat Versus Placebo in Nonhospitalized Adults With Mild-to-Moderate Coronavirus Disease 2019: A Randomized Controlled Phase 2 Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
    Trial
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Androgen Drives the Expression of SARS-CoV-2 Entry Proteins in Sinonasal Tissue.Journal of clinical and translational pathology · 2023
    Article
  8. Article
  9. Article
  10. 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

10 authors at 2 institutions in 1 country.

Wenrui GuoDepartment of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, UK.
Linsey M PorterDepartment of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, UK.
Thomas Wm CrozierDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.
Matthew CoatesDepartment of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, UK.
Akhilesh JhaDepartment of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, UK.
Mikel McKieMedical Research Council, Biostatistic Unit, Cambridge, UK.
James A NathanDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.ORCID 0000-0002-0248-1632
Paul J LehnerDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.
Edward Jd GreenwoodDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK fm319@cam.ac.uk.ORCID 0000-0002-5224-0263
Frank McCaughanDepartment of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, UK ejdg2@cam.ac.uk.ORCID 0000-0002-8012-7524
University of Cambridge · GBMedical Research Council · GB

Funding

Medical Research Council MR/V011561/1Wellcome Trust 210688/Z/18/Z
6 · The paper itself

Abstract

backgroundThere are limited effective prophylactic/early treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Viral entry requires spike protein binding to the angiotensin-converting enzyme-2 receptor and cleavage by transmembrane serine protease 2 (TMPRSS2), a cell surface serine protease. Targeting of TMPRSS2 by either androgen blockade or direct inhibition is in clinical trials in early SARS-CoV-2 infection.

methodsWe used differentiated primary human airway epithelial cells at the air-liquid interface to test the impact of targeting TMPRSS2 on the prevention of SARS-CoV-2 infection.

resultsWe first modelled the systemic delivery of compounds. Enzalutamide, an oral androgen receptor antagonist, had no impact on SARS-CoV-2 infection. By contrast, camostat mesylate, an orally available serine protease inhibitor, blocked SARS-CoV-2 entry. However, oral camostat is rapidly metabolised in the circulation, with poor airway bioavailability. We therefore modelled local airway administration by applying camostat to the apical surface of differentiated airway cultures. We demonstrated that a brief exposure to topical camostat effectively restricts SARS-CoV-2 infection.

conclusionThese experiments demonstrate a potential therapeutic role for topical camostat for pre- or post-exposure prophylaxis of SARS-CoV-2, which can now be evaluated in a clinical trial.

Indexed as

Administration, TopicalAndrogensAngiotensin-Converting Enzyme 2Antiviral AgentsCells, CulturedCOVID-19Epithelial CellsEstersGene ExpressionGoblet CellsGuanidinesHost-Pathogen InteractionsHumansRespiratory MucosaSARS-CoV-2Serine EndopeptidasesACE2 protein, humanAndrogensAngiotensin-Converting Enzyme 2Antiviral AgentscamostatEstersGuanidinesSerine EndopeptidasesSerine Proteinase InhibitorsTMPRSS2 protein, human

Identifiers

PMID35110354
PMCPMC8814636
OpenAlexW4210778472

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.