ArticleProceedings of the National Academy of Sciences of the United States of America1999
Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
147 citing papers in PubMed, 316 citations in OpenAlex.
- In vitro antiviral activity and single-dose pharmacokinetics in humans of a novel, orally bioavailable inhibitor of human rhinovirus 3C protease.Antimicrobial agents and chemotherapy · 2005Trial
- Pharmacokinetics and safety of an antirhinoviral agent, ruprintrivir, in healthy volunteers.Antimicrobial agents and chemotherapy · 2002Trial
- The pivotal role of β-lactone stereochemistry in the development of SARS-CoV-2 MProtein science : a publication of the Protein Society · 2026Article
- Tulane virus protease as a structural surrogate for inhibitor screening of human norovirus proteases.Journal of virology · 2026Article
- Structural insights into the antiviral efficacy of AG7404 against human rhinovirus 3C proteases.IUCrJ · 2026Article
- Viral interference of nucleocytoplasmic transport.The Journal of biological chemistry · 2025Review
- Antiviral candidates for enterovirus 71: targeting viral proteome and stage-specific lifecycle interventions.Virology journal · 2025Review
- Structural basis for 3C and 3CD recruitment by enteroviral genomes during negative-strand RNA synthesis.Nature communications · 2025Article
- Conformational flexibility is a critical factor in designing broad-spectrum human norovirus protease inhibitors.Journal of virology · 2025Article
- Paradigms of convergent evolution in enzymes.The FEBS journal · 2025Article
- Article
- Elucidating the structural dynamics induced by active site mutations in 3C protease of foot-and-mouth disease virus.PloS one · 2025Article
- Antiviral Development for the Polio Endgame: Current Progress and Future Directions.Pathogens (Basel, Switzerland) · 2024Review
- A Structural Investigation of the Interaction between a GC-376-Based Peptidomimetic PROTAC and Its Precursor with the Viral Main Protease of Coxsackievirus B3.Biomolecules · 2024Article
- CONFORMATIONAL FLEXIBILITY IS A CRITICAL FACTOR IN DESIGNING BROAD-SPECTRUM HUMAN NOROVIRUS PROTEASE INHIBITORS.bioRxiv : the preprint server for biology · 2024Article
- Elucidating the Substrate Envelope of Enterovirus 68-3C Protease: Structural Basis of Specificity and Potential Resistance.Viruses · 2024Article
- An efficientJournal of virology · 2024Article
- Potent small molecule inhibitors against the 3C protease of foot-and-mouth disease virus.Microbiology spectrum · 2024Article
- An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations.Science translational medicine · 2024Article
- Phytochemicals: Promising Inhibitors of Human Rhinovirus Type 14 3C Protease as a Strategy to Fight the Common Cold.Current topics in medicinal chemistry · 2024Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human rhinoviruses, the most important etiologic agents of the common cold, are messenger-active single-stranded monocistronic RNA viruses that have evolved a highly complex cascade of proteolytic processing events to control viral gene expression and replication. Most maturation cleavages within the precursor polyprotein are mediated by rhinovirus 3C protease (or its immediate precursor, 3CD), a cysteine protease with a trypsin-like polypeptide fold. High-resolution crystal structures of the enzyme from three viral serotypes have been used for the design and elaboration of 3C protease inhibitors representing different structural and chemical classes. Inhibitors having alpha,beta-unsaturated carbonyl groups combined with peptidyl-binding elements specific for 3C protease undergo a Michael reaction mediated by nucleophilic addition of the enzyme's catalytic Cys-147, resulting in covalent-bond formation and irreversible inactivation of the viral protease. Direct inhibition of 3C proteolytic activity in virally infected cells treated with these compounds can be inferred from dose-dependent accumulations of viral precursor polyproteins as determined by SDS/PAGE analysis of radiolabeled proteins. Cocrystal-structure-assisted optimization of 3C-protease-directed Michael acceptors has yielded molecules having extremely rapid in vitro inactivation of the viral protease, potent antiviral activity against multiple rhinovirus serotypes and low cellular toxicity. Recently, one compound in this series, AG7088, has entered clinical trials.
Indexed as
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.