Evidence map›Paper›PMID 34962926›Full record

ArticlePLoS biology2021

A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets.

Annika Kratzel, Jenna N Kelly, Philip V'kovski, Jasmine Portmann, Yannick Brüggemann, Daniel Todt, Nadine Ebert, Neeta Shrestha, Philippe Plattet, Claudia A Staab-Weijnitz and 6 more

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

44 citing papers in PubMed, 64 citations in OpenAlex.

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  12. The Pestivirus RNase EViruses · 2024
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  18. SARS-CoV-2 biology and host interactions.Nature reviews. Microbiology · 2024
    Review
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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 4 institutions in 2 countries.

Annika KratzelInstitute of Virology and Immunology, Bern and Mittelhäusern, Switzerland.ORCID 0000-0001-8468-4742
Jenna N KellyInstitute of Virology and Immunology, Bern and Mittelhäusern, Switzerland.ORCID 0000-0001-7265-2233
Philip V'kovskiInstitute of Virology and Immunology, Bern and Mittelhäusern, Switzerland.ORCID 0000-0002-8366-1220
Jasmine PortmannInstitute of Virology and Immunology, Bern and Mittelhäusern, Switzerland.
Yannick BrüggemannDepartment for Molecular & Medical Virology, Ruhr-Universität Bochum, Germany.
Daniel TodtEuropean Virus Bioinformatics Center, Jena, Germany.ORCID 0000-0002-3564-1014
Nadine EbertInstitute of Virology and Immunology, Bern and Mittelhäusern, Switzerland.
Neeta ShresthaDivision of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Philippe PlattetDivision of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Claudia A Staab-WeijnitzComprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz-Center Munich, Member of the German Center of Lung Research (DZL), Munich, Germany.ORCID 0000-0002-1211-7834
Albrecht von BrunnMax von Pettenkofer-Institute, Ludwig-Maximilians-Universität München, Munich, Germany.
Eike SteinmannDepartment for Molecular & Medical Virology, Ruhr-Universität Bochum, Germany.
Ronald DijkmanInstitute of Virology and Immunology, Bern and Mittelhäusern, Switzerland.ORCID 0000-0003-0320-2743
Gert ZimmerInstitute of Virology and Immunology, Bern and Mittelhäusern, Switzerland.ORCID 0000-0002-2708-2507
Stephanie PfaenderDepartment for Molecular & Medical Virology, Ruhr-Universität Bochum, Germany.ORCID 0000-0002-3957-5448
Volker ThielInstitute of Virology and Immunology, Bern and Mittelhäusern, Switzerland.
University of Bern · CHRuhr University Bochum · DEGerman Center for Infection Research · DEGerman Center for Lung Research · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Over the past 20 years, 3 highly pathogenic human coronaviruses (HCoVs) have emerged-Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and, most recently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-demonstrating that coronaviruses (CoVs) pose a serious threat to human health and highlighting the importance of developing effective therapies against them. Similar to other viruses, CoVs are dependent on host factors for their survival and replication. We hypothesized that evolutionarily distinct CoVs may exploit similar host factors and pathways to support their replication cycles. Herein, we conducted 2 independent genome-wide CRISPR/Cas-9 knockout (KO) screens to identify MERS-CoV and HCoV-229E host dependency factors (HDFs) required for HCoV replication in the human Huh7 cell line. Top scoring genes were further validated and assessed in the context of MERS-CoV and HCoV-229E infection as well as SARS-CoV and SARS-CoV-2 infection. Strikingly, we found that several autophagy-related genes, including TMEM41B, MINAR1, and the immunophilin FKBP8, were common host factors required for pan-CoV replication. Importantly, inhibition of the immunophilin protein family with the compounds cyclosporine A, and the nonimmunosuppressive derivative alisporivir, resulted in dose-dependent inhibition of CoV replication in primary human nasal epithelial cell cultures, which recapitulate the natural site of virus replication. Overall, we identified host factors that are crucial for CoV replication and demonstrated that these factors constitute potential targets for therapeutic intervention by clinically approved drugs.

Indexed as

CRISPR-Cas SystemsAntiviral AgentsAutophagyGene Knockdown TechniquesHost-Pathogen InteractionsHumansMiddle East Respiratory Syndrome CoronavirusSARS-CoV-2Virus ReplicationAntiviral Agents

Identifiers

PMID34962926
PMCPMC8741300
OpenAlexW4225699259

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.