ArticlePLoS pathogens2022
Ubiquitin variants potently inhibit SARS-CoV-2 PLpro and viral replication via a novel site distal to the protease active site.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Targeting SARS-CoV-2 Non-Structural Proteins: A Blueprint for Next-Generation Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Structural Basis and Inhibitor Development of SARS-CoV-2 Papain-like Protease.Molecules (Basel, Switzerland) · 2026Review
- Rewriting the viral script: post-translational modifications orchestrating SARS-CoV-2 pathogenesis and immune evasion.Frontiers in microbiology · 2026Review
- A KRASMolecular therapy. Oncology · 2025Article
- Structural and functional insights into Ubl domain-mediated regulation of SARS-CoV-2 PLpro.Biology direct · 2025Article
- Identification of SARS-CoV-2 Main Protease Cleavage Sites in Bovine β-Casein.International journal of molecular sciences · 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
- Analysis of Structures of SARS-CoV-2 Papain-like Protease Bound with Ligands Unveils Structural Features for Inhibiting the Enzyme.Molecules (Basel, Switzerland) · 2025Review
- Suppressing Tymovirus replication in plants using a variant of ubiquitin.PLoS pathogens · 2025Article
- Native Mass Spectrometry Reveals Binding Interactions of SARS-CoV-2 PLpro with Inhibitors and Cellular Targets.ACS infectious diseases · 2024Article
- Viral deubiquitinating proteases and the promising strategies of their inhibition.Virus research · 2024Review
- Deubiquitinating activity of SARS-CoV-2 papain-like protease does not influence virus replication or innate immune responses in vivo.PLoS pathogens · 2024Article
- Article
- Protein Quality Control Systems and ER Stress as Key Players in SARS-CoV-2-Induced Neurodegeneration.Cells · 2024Review
- Isolation and Genomic Characteristics of a Novel Pathogenicity Type I Feline Coronavirus in Mainland China.Transboundary and emerging diseases · 2024Article
- What Strengthens Protein-Protein Interactions: Analysis and Applications of Residue Correlation Networks.Journal of molecular biology · 2023Article
- The role of IBV PL1pro in virus replication and suppression of host innate immune responses.BMC veterinary research · 2023Article
- Mass spectrometric assays monitoring the deubiquitinase activity of the SARS-CoV-2 papain-like protease inform on the basis of substrate selectivity and have utility for substrate identification.Bioorganic & medicinal chemistry · 2023Article
- Ubiquitin Engineering for Interrogating the Ubiquitin-Proteasome System and Novel Therapeutic Strategies.Cells · 2023Review
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 4 countries.
Funding
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has made it clear that combating coronavirus outbreaks benefits from a combination of vaccines and therapeutics. A promising drug target common to all coronaviruses-including SARS-CoV, MERS-CoV, and SARS-CoV-2-is the papain-like protease (PLpro). PLpro cleaves part of the viral replicase polyproteins into non-structural protein subunits, which are essential to the viral replication cycle. Additionally, PLpro can cleave both ubiquitin and the ubiquitin-like protein ISG15 from host cell substrates as a mechanism to evade innate immune responses during infection. These roles make PLpro an attractive antiviral drug target. Here we demonstrate that ubiquitin variants (UbVs) can be selected from a phage-displayed library and used to specifically and potently block SARS-CoV-2 PLpro activity. A crystal structure of SARS-CoV-2 PLpro in complex with a representative UbV reveals a dimeric UbV bound to PLpro at a site distal to the catalytic site. Yet, the UbV inhibits the essential cleavage activities of the protease in vitro and in cells, and it reduces viral replication in cell culture by almost five orders of magnitude.
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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.