ArticleNature communications2023
Potent and selective covalent inhibition of the papain-like protease from SARS-CoV-2.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55citing papers in PubMed
19.6field-weighted citation impact, top 1% of its field
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Who cites it
55 citing papers in PubMed, 89 citations in OpenAlex.
- Hitting Coronaviruses Where It Hurts: Antiviral Strategies Targeting Viral Proteins.ChemMedChem · 2026Review
- Substrate-Selective Inhibition of the SARS-CoV-2 Papain-Like Protease: Inhibition of Hydrolysis of Human Over Viral Substrates.Chemistry (Weinheim an der Bergstrasse, Germany) · 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
- Discovery of novel druggable binding pockets on SARS-CoV-2 PLpro via fragment screening and insights for structure-based inhibitor design.The Journal of biological chemistry · 2026Article
- Targeting SARS-CoV-2 Non-Structural Proteins: A Blueprint for Next-Generation Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Inhibitors Targeting SARS-CoV-2 Papain-Like Protease: Screening, Design, Synthesis, and Biological Evaluation.ChemMedChem · 2026Article
- Discovery of the SARS-CoV-2 Papain-Like Protease Inhibitor MR1-114: From Structure-Based Design toJournal of medicinal chemistry · 2026Article
- Discovery of Spiro[chromane-2,4'-piperidine] Derivatives as Irreversible Inhibitors of SARS-CoV-2 Papain-like Protease.Journal of medicinal chemistry · 2026Article
- Shaping Antimalarials: A Geometry-First Approach toJournal of medicinal chemistry · 2026Article
- Structural Basis and Inhibitor Development of SARS-CoV-2 Papain-like Protease.Molecules (Basel, Switzerland) · 2026Review
- YL1004 is a SARS-CoV-2 papain-like protease inhibitor with immunomodulatory and antiviral activity in mice.Nature communications · 2026Article
- Discovery of Fragment-Based Inhibitors of SARS-CoV-2 PLJournal of medicinal chemistry · 2026Article
- In Silico Optimization of Inhibitors of the 3-Chymotrypsin-like Protease of SARS-CoV-2.Life (Basel, Switzerland) · 2025Article
- Chasing allosteric inhibition of the SARS-CoV-2 PLpro via molecular dynamics simulations with flooding fragments (MDFFr).Journal of computer-aided molecular design · 2025Article
- SARS-CoV‑2 Papain-Like Protease Inhibitors Based on Naphthalen-1-ylethanamine and Halogenated Benzene Moieties.ACS omega · 2025Article
- Screening of Medicines for Malaria Venture Open Boxes Identifies Potent SARS-CoV‑2 Papain-like Protease (PLACS omega · 2025Article
- Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of the mitophagy regulator USP30.Nature structural & molecular biology · 2025Article
- PLpro Inhibitors as a Potential Treatment for COVID-19.Biomedicines · 2025Article
- Inhibiting Infectious Bronchitis Virus PLpro Using Ubiquitin Variants.International journal of molecular sciences · 2025Article
- Identification of naturally occurring drug-resistant mutations of SARS-CoV-2 papain-like protease.Nature communications · 2025Article
Corrections and comments
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Authors and funding
33 authors at 13 institutions in 1 country.
Brian C Sanders *Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA. sandersbc@ornl.gov.ORCID 0000-0001-9754-1687
Suman Pokhrel *Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-2258-8768
Audrey D LabbeBiosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
Irimpan I MathewsStanford Synchrotron Radiation Lightsource, Menlo Park, CA, USA.ORCID 0000-0001-6254-3519
Connor J CooperBiosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
Russell B DavidsonBiosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
Gwyndalyn PhillipsNeutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA.ORCID 0000-0001-5858-3825
Kevin L WeissNeutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA.ORCID 0000-0002-6486-8007
Qiu ZhangNeutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
Hugh O'NeillNeutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA.ORCID 0000-0003-2966-5527
Manat KaurDepartment of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Jurgen G SchmidtB-11 Bioenergy and Biome Sciences, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.ORCID 0000-0002-8192-9940
Walter ReichardDepartment of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA.
Surekha SurendranathanRegional Biocontainment Laboratory, University of Tennessee Health Science Center, Memphis, TN, USA.
Jyothi ParvathareddyRegional Biocontainment Laboratory, University of Tennessee Health Science Center, Memphis, TN, USA.
Lexi PhillipsInstitute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
Christopher RainvilleProgenra Inc., Malvern, PA, USA.
David E SternerProgenra Inc., Malvern, PA, USA.
Desigan KumaranBiology Department, Brookhaven National Laboratory, Upton, NY, USA.
Babak AndiCenter for BioMolecular Structure, National Synchrotron Light Source II, Brookhaven National Laboratory, Upton, NY, USA.ORCID 0000-0002-7666-639X
Gyorgy BabniggCenter for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-9838-1803
Nigel W MoriartyMolecular Biosciences and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.ORCID 0000-0001-8857-9464
Paul D AdamsMolecular Biosciences and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.ORCID 0000-0001-9333-8219
Andrzej JoachimiakCenter for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL, USA.ORCID 0000-0003-2535-6209
Brett L HurstInstitute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.ORCID 0000-0003-1025-5878
Suresh KumarProgenra Inc., Malvern, PA, USA.ORCID 0000-0002-1940-772X
Tauseef R ButtProgenra Inc., Malvern, PA, USA.
Colleen B JonssonDepartment of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA.ORCID 0000-0002-2640-7672
Lori FerrinsDepartment of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.ORCID 0000-0001-8992-0919
Soichi WakatsukiDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA. soichi.wakatsuki@stanford.edu.ORCID 0000-0001-5896-7968
Stephanie GalanieBiosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA.ORCID 0000-0001-5712-2568
Martha S HeadJoint Institute for Biological Sciences, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
Jerry M ParksBiosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA. parksjm@ornl.gov.ORCID 0000-0002-3103-9333
Oak Ridge National Laboratory · USProgenra (United States) · USUniversity of Tennessee Health Science Center · USArgonne National Laboratory · USBrookhaven National Laboratory · USLawrence Berkeley National Laboratory · USStanford Synchrotron Radiation Lightsource · USUtah State University · USLos Alamos National Laboratory · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USNortheastern University · USSLAC National Accelerator Laboratory · USStanford University · US
Funding
A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Ritimukta Sarangi · 2020 to 2026
$43.3MTO PROVIDE SCIENTIFIC SUPPORT TO THE CENTERS FOR RESEARCH ON STRUCTURAL BIOLOGY OF INFECTIOUS DISEASES.75N93022C00035 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SATCHELL, KARLA · 2022 to 2025
$20.7MNIAID NIH HHS 75N93022C00035NIAID NIH HHS HHSN272201700060CNIGMS NIH HHS P30 GM133894
Abstract
Direct-acting antivirals are needed to combat coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The papain-like protease (PLpro) domain of Nsp3 from SARS-CoV-2 is essential for viral replication. In addition, PLpro dysregulates the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 protein from host proteins. As a result, PLpro is a promising target for inhibition by small-molecule therapeutics. Here we design a series of covalent inhibitors by introducing a peptidomimetic linker and reactive electrophile onto analogs of the noncovalent PLpro inhibitor GRL0617. The most potent compound inhibits PLpro with k
Indexed as
COVID-19Hepatitis C, ChronicAnimalsAntiviral AgentsHumansMammalsPapainPeptide HydrolasesProtease InhibitorsSARS-CoV-2Antiviral AgentsPapainPeptide HydrolasesProtease Inhibitors
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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.