Evidence map›Paper›PMID 34535662›Full record

ArticleNature communications2021

A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses.

Joep Beumer, Maarten H Geurts, Mart M Lamers, Jens Puschhof, Jingshu Zhang, Jelte van der Vaart, Anna Z Mykytyn, Tim I Breugem, Samra Riesebosch, Debby Schipper and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 2 pooled it
4.6field-weighted citation impact, top 4% 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

70 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.

  1. Pooled it
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  9. TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026
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  14. Parabiosis, Assembloids, Organoids (PAO).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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10 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 2 institutions in 1 country.

Joep Beumer *Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, Netherlands.
Maarten H Geurts *Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, Netherlands.
Mart M Lamers *Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
Jens PuschhofOncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, Netherlands.
Jingshu ZhangViroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
Jelte van der VaartOncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, Netherlands.ORCID 0000-0002-4126-8420
Anna Z MykytynViroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
Tim I BreugemViroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
Samra RieseboschViroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
Debby SchipperViroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.ORCID 0000-0001-6449-4765
Petra B van den DoelViroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
Wim de LauOncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, Netherlands.
Cayetano Pleguezuelos-ManzanoOncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, Netherlands.ORCID 0000-0003-4676-9838
Georg BusslingerOncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, Netherlands.ORCID 0000-0002-7851-9895
Bart L HaagmansViroscience Department, Erasmus Medical Center, Rotterdam, Netherlands. b.haagmans@erasmusmc.nl.ORCID 0000-0001-6221-2015
Hans CleversOncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, Netherlands. h.clevers@hubrecht.eu.ORCID 0000-0002-3077-5582
Royal Netherlands Academy of Arts and Sciences · NLErasmus MC · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Genetic screens are often performed in transformed cell lines that poorly represent viral target cells in vivo, leading to discoveries that may not be translated to the clinic. Intestinal organoids are increasingly used to model human disease and are amenable to genetic engineering. To discern which host factors are reliable anti-coronavirus therapeutic targets, we generate mutant clonal IOs for 19 host genes previously implicated in coronavirus biology. We verify ACE2 and DPP4 as entry receptors for SARS-CoV/SARS-CoV-2 and MERS-CoV respectively. SARS-CoV-2 replication in IOs does not require the endosomal Cathepsin B/L proteases, but specifically depends on the cell surface protease TMPRSS2. Other TMPRSS family members were not essential. The newly emerging coronavirus variant B.1.1.7, as well as SARS-CoV and MERS-CoV similarly depended on TMPRSS2. These findings underscore the relevance of non-transformed human models for coronavirus research, identify TMPRSS2 as an attractive pan-coronavirus therapeutic target, and demonstrate that an organoid knockout biobank is a valuable tool to investigate the biology of current and future emerging coronaviruses.

Indexed as

Biological Specimen BanksCoronavirusCRISPR-Cas SystemsAngiotensin-Converting Enzyme 2Cell LineCOVID-19Dipeptidyl Peptidase 4HumansMiddle East Respiratory Syndrome CoronavirusOrganoidsSARS-CoV-2Serine EndopeptidasesTranscriptomeVirus ReplicationACE2 protein, humanAngiotensin-Converting Enzyme 2Dipeptidyl Peptidase 4DPP4 protein, humanSerine EndopeptidasesTMPRSS2 protein, human

Identifiers

PMID34535662
PMCPMC8448725
OpenAlexW3199389718

What OpenQuestion holds

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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.