ArticleJournal of virology2005
The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity.
Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 370 papers.
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Who cites it
370 citing papers in PubMed, 608 citations in OpenAlex.
- 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
- Discovery of a [4Fe-4S] cluster in the PRRSV Nsp1α leader protease reveals host-virus interplay in its downstream functions.Science advances · 2026Article
- Structural analysis of the flexibility of the Ubl2 domain within the papain-like protease of SARS-CoV-2.Acta crystallographica. Section F, Structural biology communications · 2026Article
- Discovery of the SARS-CoV-2 Papain-Like Protease Inhibitor MR1-114: From Structure-Based Design toJournal of medicinal chemistry · 2026Article
- Fecal metatranscriptomics and virus isolation reveal picornavirus diversity and evolution in Japanese wild boars and pigs.Scientific reports · 2026Article
- SARS-CoV-2 nonstructural protein 3 remodels the phosphorylation of target proteins via protein-protein interactions.Microbiology spectrum · 2026Article
- Molecular mechanisms of protease precursor autoprocessing of RNA viruses: a comprehensive review.Virology journal · 2026Review
- Quinazolinone based broad-spectrum antiviral molecules: design, synthesis, in silico studies and biological evaluation.Molecular diversity · 2026Article
- Affinity of drug candidates binding to SARS-CoV-2 PLpro assessed using a generalized-ensemble method.Scientific reports · 2026Article
- Discovery of a [4Fe-4S] cluster in the PRRSV Nsp1α leader protease reveals host-virus interplay in its downstream functions.bioRxiv : the preprint server for biology · 2026Article
- 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
- 1,2,4-Thiadiazolidin-3,5-Diones as Inhibitors of Cysteine Proteases.Molecules (Basel, Switzerland) · 2025Article
- The ORF1ab of Feline Coronavirus Plays a Critical Role in Regulating the Innate Immune Response.Viruses · 2025Article
- Integrating Molecular Dynamics, Molecular Docking, and Machine Learning for Predicting SARS-CoV-2 Papain-like Protease Binders.Molecules (Basel, Switzerland) · 2025Article
- Inhibiting Infectious Bronchitis Virus PLpro Using Ubiquitin Variants.International journal of molecular sciences · 2025Article
- Structure-Based Design and In-Silico Evaluation of Computationally Proposed Curcumin Derivatives as Potential Inhibitors of the Coronaviral PLpro Enzymes.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Comparative Interactome Profiling of Nonstructural Protein 3 Across SARS-CoV-2 Variants Emerged During the COVID-19 Pandemic.Viruses · 2025Article
- Identifying Inhibitor-SARS-CoV2-3CLMolecules (Basel, Switzerland) · 2025Article
310 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Replication of the genomic RNA of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by replicase polyproteins that are processed by two viral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro). Previously, we showed that SARS-CoV PLpro processes the replicase polyprotein at three conserved cleavage sites. Here, we report the identification and characterization of a 316-amino-acid catalytic core domain of PLpro that can efficiently cleave replicase substrates in trans-cleavage assays and peptide substrates in fluorescent resonance energy transfer-based protease assays. We performed bioinformatics analysis on 16 papain-like protease domains from nine different coronaviruses and identified a putative catalytic triad (Cys1651-His1812-Asp1826) and zinc-binding site. Mutagenesis studies revealed that Asp1826 and the four cysteine residues involved in zinc binding are essential for SARS-CoV PLpro activity. Molecular modeling of SARS-CoV PLpro suggested that this catalytic core may also have deubiquitinating activity. We tested this hypothesis by measuring the deubiquitinating activity of PLpro by two independent assays. SARS CoV-PLpro hydrolyzed both diubiquitin and ubiquitin-7-amino-4-methylcoumarin (AMC) substrates, and hydrolysis of ubiquitin-AMC is approximately 180-fold more efficient than hydrolysis of a peptide substrate that mimics the PLpro replicase recognition sequence. To investigate the critical determinants recognized by PLpro, we performed site-directed mutagenesis on the P6 to P2' residues at each of the three PLpro cleavage sites. We found that PLpro recognizes the consensus cleavage sequence LXGG, which is also the consensus sequence recognized by cellular deubiquitinating enzymes. This similarity in the substrate recognition sites should be considered during the development of SARS-CoV PLpro inhibitors.
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Registered trials
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.