ArticleScience (New York, N.Y.)2021
Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2.
Open access · hybridAbstract read
In one paragraph
Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
150citing papers in PubMed, 1 pooled it
13.9field-weighted citation impact, top 1% of its field
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.
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.
Who cites it
150 citing papers in PubMed, 1 synthesis or guideline pooled it, 248 citations in OpenAlex.
- A systematic review on impact of SARS-CoV-2 infection.Microbiological research · 2023Pooled it
- Identification of potential SARS-CoV-2 MJournal of computer-aided molecular design · 2026Article
- Native Label-Free Spectral Biochemical Fingerprinting of an Enveloped Mammalian RNA Virus Reveals Mode of Action of a Virucidal Drug.Small methods · 2026Article
- Recent Advances in the Design of Inhibitors Targeting the Viral Entry and Replication of the SARS-CoV-2 Virus, Driven by In Silico Approaches.Molecules (Basel, Switzerland) · 2026Review
- Design, Synthesis, and Evaluation of Novel Thiazole-Based Peptidomimetic Compounds as Potent SARS-CoV-2 Main Protease Covalent Inhibitors.ACS infectious diseases · 2026Article
- Inhibitory effects and structural analysis of drug candidate PF-07817883 against coronaviral main proteases (MJournal of structural biology: X · 2026Article
- A Novel Covalent Inhibitor Fragment for the SARS-CoV-2 Main Protease Identified by Target-Specific Deep Learning.ACS chemical biology · 2026Article
- Structure- and Ligand-Based Discovery of Novel 3-Chymotrypsin-Like Protease Nonpeptidomimetic Hits.ChemMedChem · 2026Article
- Next-generation inhibitors of SARS-CoV-2 MNature communications · 2026Article
- Phloretin targeting the 3CLpro Cys144 exhibits broad-spectrum antiviral activity against swine enteric coronavirus.Virologica Sinica · 2026Article
- Mutation-Induced Resistance of SARS-CoV-2 MInternational journal of molecular sciences · 2026Article
- Leak Proof PDBBind: A Reorganized Data Set of Protein-Ligand Complexes for More Generalizable Binding Affinity Prediction.The journal of physical chemistry. B · 2026Article
- Chromene-Thiazole Derivatives as Potential SARS-CoV‑2 MACS omega · 2025Article
- A KSHV-targeted small molecule efficiently blocks SARS-CoV-2 infection via inhibiting expression of EGFR and Cyclin A2.Emerging microbes & infections · 2025Article
- Polaris Challenge: Data-Driven Priors to Improve Docking for Pose Prediction.Journal of chemical information and modeling · 2025Article
- Integrating population-level and cell-based signatures for drug repositioning.Bioinformatics (Oxford, England) · 2025Article
- SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity.Nature communications · 2025Article
- Protein Engineering for Spatiotemporally Resolved Cellular Monitoring.Annual review of analytical chemistry (Palo Alto, Calif.) · 2025Review
- A new paradigm for drug discovery in the treatment of complex diseases: drug discovery and optimization.Chinese medicine · 2025Review
- Dihydropyrimidine-2-thione derivatives as SARS-CoV-2 main protease inhibitors: synthesis, SAR andRSC advances · 2025Article
90 more citing papers are in PubMed but not listed here.
Corrections and comments
- Update of
Authors and funding
38 authors at 9 institutions in 2 countries.
Nir DraymanPritzker School for Molecular Engineering, The University of Chicago, Chicago, IL, USA. tays@uchicago.edu nirdra@uchicago.edu.ORCID 0000-0003-4460-9558
Jennifer K DeMarcoCenter for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY, USA.ORCID 0000-0003-4807-6250
Krysten A JonesDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.ORCID 0000-0003-0711-5516
Saara-Anne AziziDepartment of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.ORCID 0000-0002-9226-9917
Heather M FroggattInstitut Pasteur, Viral Populations and Pathogenesis Unit, Centre National de la Recherche Scientifique UMR 3569, Paris, France.ORCID 0000-0001-7785-0976
Kemin TanDepartment of Medicine, Division of Immunobiology, Larner College of Medicine, University of Vermont, Burlington, VT, USA.ORCID 0000-0002-4003-7903
Natalia Ivanovna MaltsevaDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-2871-465X
Siquan ChenDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.
Vlad NicolaescuDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-6347-0232
Steve DvorkinDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.
Kevin FurlongDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.
Rahul S KathayatDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-9159-2413
Mason R FirpoPritzker School for Molecular Engineering, The University of Chicago, Chicago, IL, USA.
Vincent MastrodomenicoDepartment of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
Emily A BruceCellular Screening Center, The University of Chicago, Chicago, IL, USA.ORCID 0000-0001-8391-370X
Madaline M SchmidtDepartment of Medicine, Division of Immunobiology, Larner College of Medicine, University of Vermont, Burlington, VT, USA.ORCID 0000-0003-3893-3466
Robert JedrzejczakDepartment of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.ORCID 0000-0001-6375-7199
Miguel Á Muñoz-AlíaDepartment of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-6217-9451
Brooke SchusterDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-7070-6143
Vishnu NairDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-7321-1170
Kyu-Yeon HanCenter for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY, USA.ORCID 0000-0002-2561-8187
Amornrat O'BrienDepartment of Pharmaceutical Sciences, College of Pharmacy, Biophysics Core at Research Resources Center, University of Illinois at Chicago, Chicago, IL, USA.
Anastasia TomatsidouDepartment of Medicine, Division of Immunobiology, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
Bjoern MeyerInstitut Pasteur, Viral Populations and Pathogenesis Unit, Centre National de la Recherche Scientifique UMR 3569, Paris, France.ORCID 0000-0002-7903-5710
Marco VignuzziStructural Biology Center, X-ray Science Division, Argonne National Laboratory, Argonne, IL, USA.ORCID 0000-0002-4400-771X
Dominique MissiakasDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.
Jason W BottenCellular Screening Center, The University of Chicago, Chicago, IL, USA.ORCID 0000-0001-6839-0306
Christopher B BrookeDepartment of Microbiology and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, VT, USA.ORCID 0000-0002-6815-1193
Hyun LeeVaccine Testing Center, Larner College of Medicine, University of Vermont, Burlington, VT, USA.ORCID 0000-0003-2570-8120
Susan C BakerInstitut Pasteur, Viral Populations and Pathogenesis Unit, Centre National de la Recherche Scientifique UMR 3569, Paris, France.ORCID 0000-0001-6485-8143
Bryan C MounceInstitut Pasteur, Viral Populations and Pathogenesis Unit, Centre National de la Recherche Scientifique UMR 3569, Paris, France.ORCID 0000-0003-1710-5362
Nicholas S HeatonInstitut Pasteur, Viral Populations and Pathogenesis Unit, Centre National de la Recherche Scientifique UMR 3569, Paris, France.ORCID 0000-0002-5307-3428
William E SeversonDepartment of Chemistry, The University of Chicago, Chicago, IL, USA.
Kenneth E PalmerDepartment of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Bryan C DickinsonDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-9616-1911
Andrzej JoachimiakDepartment of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.ORCID 0000-0003-2535-6209
Glenn RandallCarl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.ORCID 0000-0001-7417-3615
Savaş TayDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA. tays@uchicago.edu nirdra@uchicago.edu.ORCID 0000-0002-1912-6020
University of Chicago · USUniversity of Vermont · USInstitut Pasteur · FRArgonne National Laboratory · USUniversity of Louisville · USLoyola University Chicago · USMayo Clinic in Arizona · USUniversity of Illinois Chicago · USUniversity of Illinois Urbana-Champaign · US
Funding
Using Dengue Controlled Human Infection Model to Identify Adaptive Immune Correlates of ProtectionP20GM125498 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Ellen Kozelka · 2018 to 2026
$24.9MUnderstanding the Host-Microbiome-Therapeutic Triad: Implications for Designing Alternative IntravaginalP20GM125504 · NIGMS · UNIVERSITY OF LOUISVILLE · PI Shirin Ghods · 2018 to 2026
$24.4MVermont Immunology/Infectious Diseases CenterP30GM118228 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI BUDD, RALPH C · 2016 to 2021
$6.8MMechanisms of viral proteases in coronavirus replication and pathogenesisR01AI085089 · NIAID · LOYOLA UNIVERSITY CHICAGO · PI BAKER, SUSAN C., MESECAR, ANDREW D · 2010 to 2019
$6.8MMechanisms of Protection and Durability for a Live Attenuated Tetravalent Dengue VaccineU01AI141997 · NIAID · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Sean A. Diehl, Anna Palmer Durbin · 2019 to 2026
$5.1MRapid selection approaches to understand and reprogram proteins and peptidesR35GM119840 · NIGMS · UNIVERSITY OF CHICAGO · PI Bryan Dickinson · 2016 to 2026
$4.8MUncovering and harnessing connected metabolic pathways essential to virus infection.R35GM138199 · NIGMS · LOYOLA UNIVERSITY CHICAGO · PI Bryan C Mounce · 2020 to 2026
$2.7MThe effects of influenza virus genomic heterogeneity on replication dynamics and the host responseR01AI139246 · NIAID · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI BROOKE, CHRISTOPHER BYRON · 2018 to 2022
$1.9MTherapeutic antibodies for treatment of hantavirus cardiopulmonary syndromeR41AI132047 · NIAID · CELDARA MEDICAL, LLC · PI BOTTEN, JASON W., FANGER, MICHAEL W · 2017 to 2018
$800kDeep sequencing the lymphocytic choriomeningitis arenavirus quasispecies to identify and functionally validate the molecular signature ofdefective interfering particlesR21AI154198 · NIAID · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI BOTTEN, JASON W. · 2020 to 2021
$444kNIAID NIH HHS HHSN272201700060CNIAID NIH HHS R01 AI085089NIAID NIH HHS R01 AI139246NIAID NIH HHS R21 AI154198NIAID NIH HHS R41 AI132047NIAID NIH HHS U01 AI141997NIGMS NIH HHS P20 GM125498NIGMS NIH HHS P20 GM125504NIGMS NIH HHS P30 GM118228NIGMS NIH HHS R35 GM119840NIGMS NIH HHS R35 GM138199
Abstract
There is an urgent need for antiviral agents that treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We screened a library of 1900 clinically safe drugs against OC43, a human beta coronavirus that causes the common cold, and evaluated the top hits against SARS-CoV-2. Twenty drugs significantly inhibited replication of both viruses in cultured human cells. Eight of these drugs inhibited the activity of the SARS-CoV-2 main protease, 3CLpro, with the most potent being masitinib, an orally bioavailable tyrosine kinase inhibitor. X-ray crystallography and biochemistry show that masitinib acts as a competitive inhibitor of 3CLpro. Mice infected with SARS-CoV-2 and then treated with masitinib showed >200-fold reduction in viral titers in the lungs and nose, as well as reduced lung inflammation. Masitinib was also effective in vitro against all tested variants of concern (B.1.1.7, B.1.351, and P.1).
Indexed as
COVID-19 Drug TreatmentA549 CellsAnimalsAntiviral AgentsBenzamidesCatalytic DomainCoronavirus 3C ProteasesCoronavirus OC43, HumanCOVID-19Cysteine Proteinase InhibitorsHEK293 CellsHumansInhibitory Concentration 50MiceMice, TransgenicMicrobial Sensitivity Tests3C-like proteinase, SARS-CoV-2Antiviral AgentsBenzamidesCoronavirus 3C ProteasesCysteine Proteinase InhibitorsmasitinibPiperidinesPyridinesThiazoles
Identifiers
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.