ArticleJournal of medicinal chemistry2014
X-ray structural and biological evaluation of a series of potent and highly selective inhibitors of human coronavirus papain-like proteases.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
130 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Drug targets for corona virus: A systematic review.Indian journal of pharmacologyPooled it
- 9-fluorenone-based synthetic sulfonamide compounds as dual inhibitors of SARS-CoV-2 Main-Protease and Papain-like Protease.Molecular diversity · 2026Article
- Quinazolinone based broad-spectrum antiviral molecules: design, synthesis, in silico studies and biological evaluation.Molecular diversity · 2026Article
- YL1004 is a SARS-CoV-2 papain-like protease inhibitor with immunomodulatory and antiviral activity in mice.Nature communications · 2026Article
- Discovery of SARS-CoV-2 PLpro inhibitors and RIPK1 inhibitors with synergistic antiviral efficacy in a mouse COVID-19 model.Acta pharmaceutica Sinica. B · 2026Article
- 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
- Divergent resistance pathways amongst SARS-CoV-2 PLpro inhibitors highlight the need for scaffold diversity.PLoS pathogens · 2025Article
- Advancing the Identification of Bioactive Molecules and the Construction of a Synergistic Drug Delivery System in Combating Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A novel PLpro inhibitor improves outcomes in a pre-clinical model of long COVID.Nature communications · 2025Article
- Natural and Synthetic Coumarins as Potential Drug Candidates against SARS-CoV-2/COVID-19.Current medicinal chemistry · 2025Review
- Mutational profiling of SARS-CoV-2 papain-like protease reveals requirements for function, structure, and drug escape.Nature communications · 2024Article
- Structural basis for the bi-specificity of USP25 and USP28 inhibitors.EMBO reports · 2024Article
- Viral deubiquitinating proteases and the promising strategies of their inhibition.Virus research · 2024Review
- Screening for Active Compounds ofPharmaceuticals (Basel, Switzerland) · 2024Article
- Integrating Transcriptome and Chemical Analyses to Provide Insights into Biosynthesis of Terpenoids and Flavonoids in the Medicinal Industrial CropMolecules (Basel, Switzerland) · 2024Article
- Identification of Triazolopyrimidinyl Scaffold SARS-CoV-2 Papain-Like Protease (PLPharmaceutics · 2024Article
- Targeting SARS-CoV-2 nonstructural protein 3: Function, structure, inhibition, and perspective in drug discovery.Drug discovery today · 2024Review
- Anti-diabetic, anti-pancreatic lipase, and anti-protein glycation potential ofIn silico pharmacology · 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
70 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Structure-guided design was used to generate a series of noncovalent inhibitors with nanomolar potency against the papain-like protease (PLpro) from the SARS coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS-CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2 enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies established a more than 100-fold preference for the coronaviral enzyme over homologous human deubiquitinating enzymes (DUBs), and no significant cytotoxicity in Vero E6 and HEK293 cell lines is observed. X-ray structural analyses of inhibitor-bound crystal structures revealed subtle differences between binding modes of the initial benzodioxolane lead (15g) and the most potent analogues 3k and 3j, featuring a monofluoro substitution at para and meta positions of the benzyl ring, respectively. Finally, the less lipophilic bis(amide) 3e and methoxypyridine 5c exhibit significantly improved metabolic stability and are viable candidates for advancing to in vivo studies.
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