Evidence map›Paper›PMID 35469023›Full record

ArticleNature communications2022

Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2.

Ma'ayan Israeli, Yaara Finkel, Yfat Yahalom-Ronen, Nir Paran, Theodor Chitlaru, Ofir Israeli, Inbar Cohen-Gihon, Moshe Aftalion, Reut Falach, Shahar Rotem and 9 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 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
4.1field-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

35 citing papers in PubMed, 50 citations in OpenAlex.

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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

19 authors at 3 institutions in 1 country.

Ma'ayan Israeli *Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Yaara Finkel *Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.ORCID 0000-0002-3843-2357
Yfat Yahalom-RonenDepartment of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel.
Nir ParanDepartment of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel.ORCID 0000-0001-5143-9660
Theodor ChitlaruDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Ofir IsraeliDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Inbar Cohen-GihonDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Moshe AftalionDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Reut FalachDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Shahar RotemDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Uri EliaDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Ital NemetCentral Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Limor KlikerCentral Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Michal MandelboimCentral Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Adi Beth-DinDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Tomer IsraelyDepartment of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel.ORCID 0000-0003-0246-4477
Ofer CohenDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel.
Noam Stern-GinossarDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.ORCID 0000-0003-3583-5932
Adi Bercovich-KinoriDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel. adiki@iibr.gov.il.ORCID 0000-0002-2747-1836
Israel Institute for Biological Research · ILSheba Medical Center · ILWeizmann Institute of Science · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The global spread of SARS-CoV-2 led to major economic and health challenges worldwide. Revealing host genes essential for infection by multiple variants of SARS-CoV-2 can provide insights into the virus pathogenesis, and facilitate the development of novel therapeutics. Here, employing a genome-scale CRISPR screen, we provide a comprehensive data-set of cellular factors that are exploited by wild type SARS-CoV-2 as well as two additional recently emerged variants of concerns (VOCs), Alpha and Beta. We identified several host factors critical for SARS-CoV-2 infection, including various components belonging to the Clathrin-dependent transport pathway, ubiquitination, Heparan sulfate biogenesis and host phosphatidylglycerol biosynthesis. Comparative analysis of the different VOCs revealed the host factors KREMEN2 and SETDB1 as potential unique candidates required only to the Alpha variant. Furthermore, the analysis identified GATA6, a zinc finger transcription factor, as an essential proviral gene for all variants inspected. We show that GATA6 directly regulates ACE2 transcription and accordingly, is critical for SARS-CoV-2 cell entry. Analysis of clinical samples collected from SARS-CoV-2 infected individuals shows elevated levels of GATA6, suggesting a role in COVID-19 pathogenesis. Finally, pharmacological inhibition of GATA6 resulted in down-modulation of ACE2 and inhibition of viral infectivity. Overall, we show GATA6 may represent a target for the development of anti-SARS-CoV-2 therapeutic strategies and reaffirm the value of the CRISPR loss-of-function screens in providing a list of potential new targets for therapeutic interventions.

Indexed as

Angiotensin-Converting Enzyme 2COVID-19Clustered Regularly Interspaced Short Palindromic RepeatsGATA6 Transcription FactorHumansPeptidyl-Dipeptidase AProvirusesSARS-CoV-2Angiotensin-Converting Enzyme 2GATA6 protein, humanGATA6 Transcription FactorPeptidyl-Dipeptidase A

Identifiers

PMID35469023
PMCPMC9039069
OpenAlexW4224937204

What OpenQuestion holds

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LicenceCC BY
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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.