Evidence map›Paper›PMID 32869025›Full record

ArticlebioRxiv : the preprint server for biology2020

Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection.

Jin Wei, Mia Madel Alfajaro, Ruth E Hanna, Peter C DeWeirdt, Madison S Strine, William J Lu-Culligan, Shang-Min Zhang, Vincent R Graziano, Cameron O Schmitz, Jennifer S Chen and 17 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Jin WeiDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
Mia Madel AlfajaroDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
Ruth E HannaGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Peter C DeWeirdtGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Madison S StrineDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
William J Lu-CulliganDepartment of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT, USA.
Shang-Min ZhangDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Vincent R GrazianoDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
Cameron O SchmitzDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
Jennifer S ChenDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
Madeleine C MankowskiDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
Renata B FillerDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
Victor GasqueDepartment of Medicine, Yale School of Medicine, New Haven, CT, USA.
Fernando de MiguelDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Huacui ChenDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Kasopefoluwa OguntuyoMicrobiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Laura AbriolaYale Center for Molecular Discovery, Yale University, West Haven, CT, USA.
Yulia V SurovtsevaYale Center for Molecular Discovery, Yale University, West Haven, CT, USA.
Robert C OrchardDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Benhur LeeMicrobiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Brett LindenbachDepartment of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT, USA.
Katerina PolitiDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
David van DijkDepartment of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT, USA.
Matthew D SimonDepartment of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT, USA.
Qin YanDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
John G DoenchGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Craig B WilenDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.

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
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
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
CRISPR screens for SARS-CoV-2 Host FactorsR21AI157835 · NIAID · BROAD INSTITUTE, INC. · PI DOENCH, JOHN GERARD · 2020 to 2020
$440k
Regulation of T cell-derived cytokines in allergic airway inflammationF30HL149151 · NHLBI · YALE UNIVERSITY · PI CHEN, JENNIFER S · 2020 to 2022
$113k
NCATS NIH HHS UL1 TR001863NCI NIH HHS P50 CA121974NHLBI NIH HHS F30 HL149151NIAID NIH HHS K08 AI128043NIAID NIH HHS R01 AI087925NIAID NIH HHS R01 AI123449NIAID NIH HHS R21 AI157835NIAID NIH HHS T32 AI007019NIAID NIH HHS U19 AI133524NIDA NIH HHS F31 DA054739NIGMS NIH HHS T32 GM007205NIGMS NIH HHS T32 GM007223
6 · The paper itself

Abstract

Identification of host genes essential for SARS-CoV-2 infection may reveal novel therapeutic targets and inform our understanding of COVID-19 pathogenesis. Here we performed a genome-wide CRISPR screen with SARS-CoV-2 and identified known SARS-CoV-2 host factors including the receptor ACE2 and protease Cathepsin L. We additionally discovered novel pro-viral genes and pathways including the SWI/SNF chromatin remodeling complex and key components of the TGF-β signaling pathway. Small molecule inhibitors of these pathways prevented SARS-CoV-2-induced cell death. We also revealed that the alarmin HMGB1 is critical for SARS-CoV-2 replication. In contrast, loss of the histone H3.3 chaperone complex sensitized cells to virus-induced death. Together this study reveals potential therapeutic targets for SARS-CoV-2 and highlights host genes that may regulate COVID-19 pathogenesis.

Identifiers

PMID32869025
PMCPMC7457610

What OpenQuestion holds

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Registered trials

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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.