ArticleNature communications2016
Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Inhibiting Mrt4-rRNA interaction with fumaramidmycin-based derivatives as an antifungal strategy.Nature communications · 2026Article
- Vitamin BOrganic letters · 2025Article
- Antiviral and immunoregulatory effects of curcumin on coxsackievirus B3-infected hepatitis.Virus research · 2023Article
- Technologies for Direct Detection of Covalent Protein-Drug Adducts.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Rational Tuning of the Reactivity of Three-Membered Heterocycle Ring Openings via SChemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- In Silico Drug Repositioning to Target the SARS-CoV-2 Main Protease as Covalent Inhibitors Employing a Combined Structure-Based Virtual Screening Strategy of Pharmacophore Models and Covalent Docking.International journal of molecular sciences · 2022Article
- Proteome-Wide Profiling of the Covalent-Druggable Cysteines with a Structure-Based Deep Graph Learning Network.Research (Washington, D.C.) · 2022Article
- Chemical Evolution of Antivirals Against Enterovirus D68 through Protein-Templated Knoevenagel Reactions.Angewandte Chemie (International ed. in English) · 2021Article
- Modeling the complete kinetics of coxsackievirus B3 reveals human determinants of host-cell feedback.Cell systems · 2021Article
- Virus-Host Interactions in Foot-and-Mouth Disease Virus Infection.Frontiers in immunology · 2021Review
- Validating Enterovirus D68-2AJournal of virology · 2019Article
- The transcription factor STAT5 catalyzes Mannich ligation reactions yielding inhibitors of leukemic cell proliferation.Nature communications · 2019Article
- Vinyl sulfonamide synthesis for irreversible tetheringMedChemComm · 2019Article
- High-Throughput Kinetic Analysis for Target-Directed Covalent Ligand Discovery.Angewandte Chemie (International ed. in English) · 2018Article
- Road Map for the Structure-Based Design of Selective Covalent HCV NS3/4A Protease Inhibitors.The protein journal · 2017Review
- Protein-Templated Fragment Ligations-From Molecular Recognition to Drug Discovery.Angewandte Chemie (International ed. in English) · 2017Review
- Proteintemplat-gesteuerte Fragmentligationen - von der molekularen Erkennung zur Wirkstofffindung.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2017Article
- Protein-Templated Formation of an Inhibitor of the Blood Coagulation Factor Xa through a Background-Free Amidation Reaction.Angewandte Chemie (International ed. in English) · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme-inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases.
Identifiers
What OpenQuestion holds
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.