ArticleCell reports2021
A molecular sensor determines the ubiquitin substrate specificity of SARS-CoV-2 papain-like protease.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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Who cites it
36 citing papers in PubMed, 51 citations in OpenAlex.
- Understanding protein ISGylation, a multifaceted posttranslational modification.Cell chemical biology · 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
- Nanobodies targeting SARS-CoV-2 papain-like protease exert dual antiviral and anti-inflammatory effects.Journal of virology · 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
- Molecular mechanisms of protease precursor autoprocessing of RNA viruses: a comprehensive review.Virology journal · 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
- Structural and functional insights into Ubl domain-mediated regulation of SARS-CoV-2 PLpro.Biology direct · 2025Article
- DIG-DUBs: mechanisms and functions of ISG15 deconjugation by human and viral cross-reactive ubiquitin proteases.Biochemical Society transactions · 2025Article
- Frustration in physiology and molecular medicine.Molecular aspects of medicine · 2025Review
- Detecting SARS-CoV-2 cryptic lineages using publicly available whole genome wastewater sequencing data.PLoS pathogens · 2025Article
- Lessons learnt from broad-spectrum coronavirus antiviral drug discovery.Expert opinion on drug discovery · 2024Review
- Review
- Deubiquitinating activity of SARS-CoV-2 papain-like protease does not influence virus replication or innate immune responses in vivo.PLoS pathogens · 2024Article
- Modeling of noncovalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 considering the protein flexibility by using molecular dynamics and cross-docking.Frontiers in molecular biosciences · 2024Article
- Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2 prolonged infection.Virus evolution · 2024Article
- Local energetic frustration conservation in protein families and superfamilies.Nature communications · 2023Article
- Cellular Assays for Dynamic Quantification of Deubiquitinase Activity and Inhibition.Journal of molecular biology · 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
- An Overview on Anti-COVID-19 Drug Achievements and Challenges Ahead.ACS pharmacology & translational science · 2023Review
- An expanded lexicon for the ubiquitin code.Nature reviews. Molecular cell biology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The SARS-CoV-2 papain-like protease (PLpro) is a target for antiviral drug development. It is essential for processing viral polyproteins for replication and functions in host immune evasion by cleaving ubiquitin (Ub) and ubiquitin-like protein (Ubl) conjugates. While highly conserved, SARS-CoV-2 and SARS-CoV PLpro have contrasting Ub/Ubl substrate preferences. Using a combination of structural analyses and functional assays, we identify a molecular sensor within the S1 Ub-binding site of PLpro that serves as a key determinant of substrate specificity. Variations within the S1 sensor specifically alter cleavage of Ub substrates but not of the Ubl interferon-stimulated gene 15 protein (ISG15). Significantly, a variant of concern associated with immune evasion carries a mutation in the S1 sensor that enhances PLpro activity on Ub substrates. Collectively, our data identify the S1 sensor region as a potential hotspot of variability that could alter host antiviral immune responses to newly emerging SARS-CoV-2 lineages.
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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.