ArticleThe EMBO journal2020
Mechanism and inhibition of the papain-like protease, PLpro, of SARS-CoV-2.
Abstract read
In one paragraph
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 308 papers.
0numbers the graph read from it
0cells of the map it votes in
308citing papers in PubMed
–field-weighted citation impact
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
308 citing papers in PubMed.
- Nsp3 Ubl1-orchestrated dephosphorylation of N protein promotes coronaviral subgenomic RNA synthesis.bioRxiv : the preprint server for biology · 2026Article
- 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
- Antimicrobial peptides as computational candidates for SARS-CoV-2 papain-like protease inhibition.Scientific reports · 2026Article
- A fish-specific E3 ubiquitin ligase NHRE3 suppresses antiviral immunity by degrading ISG15 via ubiquitination.PLoS pathogens · 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
- Immunological Evaluation of mRNA-LNP Vaccines Targeting Conserved S2 and NSP3 Domains of SARS-CoV-2.Biotechnology journal · 2026Article
- Temporal Dynamics of Innate Immune Activation and Viral Interference During Sequential Co-Infection with Influenza A Virus and SARS-CoV-2: Molecular Mechanisms, Clinical Evidence, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- 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
- Global analysis of cancer cell responses to USP9X inhibition.The EMBO journal · 2026Article
- Redundant and distinct mechanisms suppress innate immune activation during SARS-CoV-2 infection.PLoS biology · 2026Article
- Discovery of the SARS-CoV-2 Papain-Like Protease Inhibitor MR1-114: From Structure-Based Design toJournal of medicinal chemistry · 2026Article
- Molecular mechanisms of protease precursor autoprocessing of RNA viruses: a comprehensive review.Virology journal · 2026Review
- Mechanistic insights into the noncovalent inhibition of SARS-CoV-2 PLpro: a multiscale computational study.Journal of computer-aided molecular design · 2026Article
- Structural Basis and Inhibitor Development of SARS-CoV-2 Papain-like Protease.Molecules (Basel, Switzerland) · 2026Review
- The Emerging Promise of Pentacyclic Triterpenoid Derivatives as Novel Antiviral Agents Against SARS-CoV-2 Variants.Molecules (Basel, Switzerland) · 2026Review
- SARS-CoV-2-host and interactions: the dual roles of E3 ubiquitin ligases and ubiquitin-like modification mechanisms in viral infection.Frontiers in immunology · 2026Review
- Chasing allosteric inhibition of the SARS-CoV-2 PLpro via molecular dynamics simulations with flooding fragments (MDFFr).Journal of computer-aided molecular design · 2025Article
- In Silico Optimization of Inhibitors of the 3-Chymotrypsin-like Protease of SARS-CoV-2.Life (Basel, Switzerland) · 2025Article
248 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors.
Theresa KlemmThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0002-2847-3550
Gregor EbertThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
Dale J CallejaThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0002-8306-0900
Cody C AllisonThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
Lachlan W RichardsonThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0001-8877-1376
Jonathan P BernardiniThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0002-5767-7624
Bernadine Gc LuThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0001-8044-9710
Nathan W KuchelThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
Christoph GrohmannThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
Yuri ShibataThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
Zhong Yan GanThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0001-5755-7780
James P CooneyThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0003-3680-4644
Marcel DoerflingerThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0001-9159-3021
Amanda E AuThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0003-3656-2673
Timothy R BlackmoreThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0001-7079-676X
Gerbrand J van der Heden van NoortOncode Institute and Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands.ORCID 0000-0001-5955-6431
Paul P GeurinkOncode Institute and Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands.
Huib OvaaOncode Institute and Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands.
Janet NewmanCommonwealth Scientific and Industrial Research Organisation (CSIRO), Biomedical Program, Parkville, Vic., Australia.ORCID 0000-0003-2666-3219
Alan Riboldi-TunnicliffeAustralian Synchrotron, ANSTO, Clayton, Vic., Australia.ORCID 0000-0003-2244-2486
Peter E CzabotarThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
Jeffrey P MitchellThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
Rebecca FelthamThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
Bernhard C LechtenbergThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0002-5674-6894
Kym N LowesThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
Grant DewsonThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0003-4251-8898
Marc PellegriniThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0003-3627-3126
Guillaume LesseneThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0002-1193-8147
David KomanderThe Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.ORCID 0000-0002-8092-4320
Funding
Department of Health | National Health and Medical Research Council (NHMRC) GNT0637350Department of Health | National Health and Medical Research Council (NHMRC) GNT1117089Department of Health | National Health and Medical Research Council (NHMRC) GNT1178122Department of Health | National Health and Medical Research Council (NHMRC) IRIISS grant 361646Department of Health | National Health and Medical Research Council (NHMRC) MRF2002119Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) Off-RoadNederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) VIDIVictorian State Government
Abstract
The SARS-CoV-2 coronavirus encodes an essential papain-like protease domain as part of its non-structural protein (nsp)-3, namely SARS2 PLpro, that cleaves the viral polyprotein, but also removes ubiquitin-like ISG15 protein modifications as well as, with lower activity, Lys48-linked polyubiquitin. Structures of PLpro bound to ubiquitin and ISG15 reveal that the S1 ubiquitin-binding site is responsible for high ISG15 activity, while the S2 binding site provides Lys48 chain specificity and cleavage efficiency. To identify PLpro inhibitors in a repurposing approach, screening of 3,727 unique approved drugs and clinical compounds against SARS2 PLpro identified no compounds that inhibited PLpro consistently or that could be validated in counterscreens. More promisingly, non-covalent small molecule SARS PLpro inhibitors also target SARS2 PLpro, prevent self-processing of nsp3 in cells and display high potency and excellent antiviral activity in a SARS-CoV-2 infection model.
Indexed as
AnimalsAntiviral AgentsBinding SitesChlorocebus aethiopsCoronavirus 3C ProteasesCrystallography, X-RayCytokinesDrug Evaluation, PreclinicalDrug RepositioningFluorescence PolarizationHEK293 CellsHumansKineticsModels, MolecularProtease InhibitorsProtein Conformation3C-like proteinase, SARS-CoV-2Antiviral AgentsCoronavirus 3C ProteasesCytokinesISG15 protein, humanProtease InhibitorsUbiquitinUbiquitinsCOVID-19ISG15papain-like proteasesmall molecule inhibitorubiquitin
Identifiers
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.