Evidence map›Paper›PMID 33784499›Full record

ArticleCell reports2021

Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication.

Gustavo Garcia, Arun Sharma, Arunachalam Ramaiah, Chandani Sen, Arunima Purkayastha, Donald B Kohn, Mark S Parcells, Sebastian Beck, Heeyoung Kim, Malina A Bakowski and 18 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
6.4field-weighted citation impact, top 3% 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

79 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.

  1. Pooled it
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  15. Investigating DNA damage caused by COVID-19 and influenza in post COVID-19.Mammalian genome : official journal of the International Mammalian Genome Society · 2025
    Article
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19 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

28 authors at 11 institutions in 2 countries.

Gustavo GarciaDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Arun SharmaBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Arunachalam RamaiahDepartment of Ecology and Evolutionary Biology, University of California, Irvine, Irvine, CA 92697, USA; Section of Cell and Developmental Biology, University of California, San Diego, San Diego, CA 92093, USA.
Chandani SenUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
Arunima PurkayasthaUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
Donald B KohnUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA.
Mark S ParcellsDepartment of Animal and Food Sciences, Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Sebastian BeckHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Heeyoung KimDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Malina A BakowskiCalibr, a division of Scripps Research Institute, 11119 North Torrey Pines Road, La Jolla, CA 92037, USA.
Melanie G KirkpatrickCalibr, a division of Scripps Research Institute, 11119 North Torrey Pines Road, La Jolla, CA 92037, USA.
Laura RivaCalibr, a division of Scripps Research Institute, 11119 North Torrey Pines Road, La Jolla, CA 92037, USA.
Karen C WolffCalibr, a division of Scripps Research Institute, 11119 North Torrey Pines Road, La Jolla, CA 92037, USA.
Brandon HanCalifornia NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Constance YuenCalifornia NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
David UlmertDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA.
Prabhat K PurbeyDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Philip ScumpiaDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Nathan BeutlerDepartment of Immunology and Microbiology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Thomas F RogersDepartment of Immunology and Microbiology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; UC San Diego Division of Infectious Diseases and Global Public Health, UC San Diego School of Medicine, La Jolla, CA 92093, USA.
Arnab K ChatterjeeCalibr, a division of Scripps Research Institute, 11119 North Torrey Pines Road, La Jolla, CA 92037, USA.
Gülsah GabrielHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Ralf BartenschlagerDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany; German Center for Infection Research, Heidelberg partner site, Heidelberg, Germany; Division Virus-Associated Carcinogenesis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Brigitte GompertsUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA.
Clive N SvendsenBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Ulrich A K BetzMerck KGaA, Darmstadt, Germany. Electronic address: ulrich.betz@merckgroup.com.
Robert D DamoiseauxDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: rdamoiseaux@mednet.ucla.edu.
Vaithilingaraja ArumugaswamiDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: varumugaswami@mednet.ucla.edu.
Scripps Research Institute · USCalifornia NanoSystems Institute · USMattel Children's Hospital · USUniversity of California, Los Angeles · USCedars-Sinai Medical Center · USLeibniz Institute of Virology (LIV) · DEGerman Cancer Research Center · DEHeidelberg University · DEMerck (Germany) · DEUniversity of California, Irvine · USUniversity of Delaware · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Metabolic and epigenetic reprogramming of vital organs in SARS-CoV-2 induced systemic toxicityR01DK132735 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARUMUGASWAMI, VAITHILINGARAJA, DEB, ARJUN · 2021 to 2023
$6.0M
Training in Advanced Heart Disease ResearchT32HL116273 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI Joshua I Goldhaber, EDUARDO MARBAN · 2013 to 2026
$5.6M
Interplay between AMPK and Hippo Signaling Regulates Ocular Antiviral Response to Zika virus infectionR01EY032149 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Vaithilingaraja Arumugaswami, Ashok Kumar · 2021 to 2026
$2.8M
Impact of Seasonal Variation in Hematocrit, NOx & ET-1 on Vascular ReactivityR21NR010361 · NINR · UNIVERSITY OF MISSOURI-COLUMBIA · PI WIPKE-TEVIS, DEIDRE D · 2008 to 2009
$401k
NCI NIH HHS P30 CA016042NEI NIH HHS R01 EY032149NHLBI NIH HHS T32 HL116273NIDDK NIH HHS R01 DK132735NINR NIH HHS R21 NR010361
6 · The paper itself

Abstract

SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified a small-molecule library of 34 of 430 protein kinase inhibitors that were capable of inhibiting the SARS-CoV-2 cytopathic effect in human epithelial cells. These drug inhibitors are in various stages of clinical trials. We detected key proteins involved in cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-damage response that are critical for SARS-CoV-2 infection. A drug-protein interaction-based secondary screen confirmed compounds, such as the ATR kinase inhibitor berzosertib and torin2 with anti-SARS-CoV-2 activity. Berzosertib exhibited potent antiviral activity against SARS-CoV-2 in multiple cell types and blocked replication at the post-entry step. Berzosertib inhibited replication of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV) as well. Our study highlights key promising kinase inhibitors to constrain coronavirus replication as a host-directed therapy in the treatment of COVID-19 and beyond as well as provides an important mechanism of host-pathogen interactions.

Indexed as

COVID-19 Drug TreatmentDNA DamageA549 CellsAnimalsAntiviral AgentsChlorocebus aethiopsCOVID-19Drug Evaluation, PreclinicalHEK293 CellsHeLa CellsHumansIsoxazolesMAP Kinase Signaling SystemMiddle East Respiratory Syndrome CoronavirusPyrazinesSARS-CoV-2Antiviral AgentsberzosertibIsoxazolesPyrazinesATR kinaseberzosertibCOVID-19DNA-damage response pathwayhigh-throughput screenmTOR-PI3K-AKT pathwaynucleoside analogsprotein kinase inhibitorsSARS-CoV-2

Identifiers

PMID33784499
PMCPMC7969873
OpenAlexW3136337343

What Socratic 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 Socratic graph.