Evidence map›Paper›PMID 33147444›Full record

ArticleCell2021

Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection.

Jin Wei, Mia Madel Alfajaro, Peter C DeWeirdt, Ruth E Hanna, William J Lu-Culligan, Wesley L Cai, Madison S Strine, Shang-Min Zhang, Vincent R Graziano, Cameron O Schmitz and 21 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 386 papers.

0numbers the graph read from it
0cells of the map it votes in
386citing papers in PubMed
11.1field-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

386 citing papers in PubMed, 579 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. The role ofFrontiers in immunology · 2026
    Review
  18. Review
  19. Review
  20. Article

326 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 6 institutions in 1 country.

Jin WeiDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
Mia Madel AlfajaroDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
Peter C DeWeirdtGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ruth E HannaGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
William J Lu-CulliganDepartment of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520, USA; Department of Cell Biology, Yale University, New Haven, CT 06520, USA; Chemical Biology Institute, Yale University, West Haven, CT 06516, USA.
Wesley L CaiDepartment of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
Madison S StrineDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
Shang-Min ZhangDepartment of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
Vincent R GrazianoDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
Cameron O SchmitzDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
Jennifer S ChenDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
Madeleine C MankowskiDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
Renata B FillerDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
Neal G RavindraCardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Computer Science, Yale University, New Haven, CT 06520, USA.
Victor GasqueCardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Computer Science, Yale University, New Haven, CT 06520, USA.
Fernando J de MiguelDepartment of Pathology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.
Ajinkya PatilDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Huacui ChenDepartment of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
Kasopefoluwa Y OguntuyoDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Laura AbriolaYale Center for Molecular Discovery, Yale University, West Haven, CT 06516, USA.
Yulia V SurovtsevaYale Center for Molecular Discovery, Yale University, West Haven, CT 06516, USA.
Robert C OrchardDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Benhur LeeDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Brett D LindenbachDepartment of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06520, USA.
Katerina PolitiDepartment of Pathology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA; Department of Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
David van DijkCardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Computer Science, Yale University, New Haven, CT 06520, USA.
Cigall KadochDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Matthew D SimonDepartment of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520, USA; Chemical Biology Institute, Yale University, West Haven, CT 06516, USA.
Qin YanDepartment of Pathology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.
John G DoenchGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: jdoench@broadinstitute.org.
Craig B WilenDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: craig.wilen@yale.edu.
Yale University · USBroad Institute · USIcahn School of Medicine at Mount Sinai · USYale Cancer Center · USDana-Farber Cancer Institute · USThe University of Texas Southwestern Medical Center · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale SPORE in Skin CancerP50CA121974 · NCI · YALE UNIVERSITY · PI RUTH HALABAN · 2006 to 2026
$43.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung CancerP50CA196530 · NCI · YALE UNIVERSITY · PI Kurt A Schalper · 2015 to 2026
$31.1M
Skill Development for Diverse Scientific Careers: A New Course Predoctoral Program in Cellular and Molecular BiologyT32GM007223 · NIGMS · YALE UNIVERSITY · PI BASERGA, SUSAN J · 1985 to 2019
$31.0M
INTERDISCIPLINARY IMMUNOLOGY TRAINING PROGRAMT32AI007019 · NIAID · YALE UNIVERSITY · PI Carrie L. Lucas, David G. Schatz · 1985 to 2026
$14.4M
Project 2: Genes required for dendritic cell responses to pathogens and T cellsU19AI133524 · NIAID · HARVARD MEDICAL SCHOOL · PI SHARPE, ARLENE H. · 2017 to 2021
$12.3M
Molecular determinants of hepatitis C virus assemblyR01AI087925 · NIAID · YALE UNIVERSITY · PI LINDENBACH, BRETT D. · 2010 to 2020
$4.1M
The role of tuft cells in norovirus pathogenesisR01AI148467 · NIAID · YALE UNIVERSITY · PI Craig Brian Wilen · 2020 to 2026
$3.9M
Yale Cancer Biology Training GrantT32CA193200 · NCI · YALE UNIVERSITY · PI PETER M GLAZER, Qin Yan · 2016 to 2026
$3.6M
Tropism, pathogenicity, and potential for zoonotic spillover of emergent henipa- and henipa-like virusesR01AI123449 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI LEE, BENHUR · 2016 to 2020
$2.7M
Role of virus-receptor interactions in determining norovirus tropism and pathogenesis in vivoK08AI128043 · NIAID · YALE UNIVERSITY · PI WILEN, CRAIG BRIAN · 2017 to 2021
$940k
NCATS NIH HHS UL1 TR001863NCI NIH HHS P50 CA121974NCI NIH HHS P50 CA196530NCI NIH HHS T32 CA193200NHLBI NIH HHS F30 HL149151NIAID NIH HHS F31 AI154739NIAID NIH HHS F31 AI54739NIAID NIH HHS K08 AI128043NIAID NIH HHS R01 AI087925NIAID NIH HHS R01 AI123449NIAID NIH HHS R01 AI148467NIAID NIH HHS R21 AI157835NIAID NIH HHS T32 AI007019NIAID NIH HHS U19 AI133524NIDA NIH HHS F31 DA054739NIDDK NIH HHS R00 DK116666NIGMS NIH HHS T32 GM007205NIGMS NIH HHS T32 GM007223
6 · The paper itself

Abstract

Identification of host genes essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may reveal novel therapeutic targets and inform our understanding of coronavirus disease 2019 (COVID-19) pathogenesis. Here we performed genome-wide CRISPR screens in Vero-E6 cells with SARS-CoV-2, Middle East respiratory syndrome CoV (MERS-CoV), bat CoV HKU5 expressing the SARS-CoV-1 spike, and vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike. We identified known SARS-CoV-2 host factors, including the receptor ACE2 and protease Cathepsin L. We additionally discovered pro-viral genes and pathways, including HMGB1 and the SWI/SNF chromatin remodeling complex, that are SARS lineage and pan-coronavirus specific, respectively. We show that HMGB1 regulates ACE2 expression and is critical for entry of SARS-CoV-2, SARS-CoV-1, and NL63. We also show that small-molecule antagonists of identified gene products inhibited SARS-CoV-2 infection in monkey and human cells, demonstrating the conserved role of these genetic hits across species. This identifies potential therapeutic targets for SARS-CoV-2 and reveals SARS lineage-specific and pan-CoV host factors that regulate susceptibility to highly pathogenic CoVs.

Indexed as

Genome-Wide Association StudyHost-Pathogen InteractionsAngiotensin-Converting Enzyme 2AnimalsCell LineChlorocebus aethiopsClustered Regularly Interspaced Short Palindromic RepeatsCoronavirusCoronavirus InfectionsCOVID-19Gene Knockout TechniquesGene Regulatory NetworksHEK293 CellsHMGB1 ProteinHumansSARS-CoV-2Angiotensin-Converting Enzyme 2HMGB1 ProteinCOVID-19CRISPR screenEpigeneticsHMGB1MERS-CoVMiddle East Respiratory SyndromeSARS-CoV-2Severe Acute Respiratory SyndromeSWI/SNF complex

Identifiers

PMID33147444
PMCPMC7574718
OpenAlexW3094597057

What OpenQuestion holds

Textmetadata
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.