Trial reportAntimicrobial agents and chemotherapy2005
In vitro antiviral activity and single-dose pharmacokinetics in humans of a novel, orally bioavailable inhibitor of human rhinovirus 3C protease.
Trial report in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 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
70 citing papers in PubMed, 134 citations in OpenAlex.
- Molecular mechanisms of protease precursor autoprocessing of RNA viruses: a comprehensive review.Virology journal · 2026Review
- Structural insights into the antiviral efficacy of AG7404 against human rhinovirus 3C proteases.IUCrJ · 2026Article
- Review
- Quercetin-3-Methyl Ether Induces Early Apoptosis to Overcome HRV1B Immune Evasion, Suppress Viral Replication, and Mitigate Inflammatory Pathogenesis.Biomolecules & therapeutics · 2025Article
- Article
- Antiviral Development for the Polio Endgame: Current Progress and Future Directions.Pathogens (Basel, Switzerland) · 2024Review
- From the "One-Molecule, One-Target, One-Disease" Concept towards Looking for Multi-Target Therapeutics for Treating Non-Polio Enterovirus (NPEV) Infections.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Elucidating the Substrate Envelope of Enterovirus 68-3C Protease: Structural Basis of Specificity and Potential Resistance.Viruses · 2024Article
- 3-chymotrypsin-like protease in SARS-CoV-2.Bioscience reports · 2024Review
- Breaking the Chain: Protease Inhibitors as Game Changers in Respiratory Viruses Management.International journal of molecular sciences · 2024Review
- An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations.Science translational medicine · 2024Article
- On the origins of SARS-CoV-2 main protease inhibitors.RSC medicinal chemistry · 2024Review
- Integrated compact regulators of protein activity enable control of signaling pathways and genome-editing in vivo.Cell discovery · 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
- Picornavirus 3C Proteins Intervene in Host Cell Processes through Proteolysis and Interactions with RNA.Viruses · 2023Review
- Vemurafenib Inhibits Acute and Chronic Enterovirus Infection by Affecting Cellular Kinase Phosphatidylinositol 4-Kinase Type IIIβ.Microbiology spectrum · 2023Article
- Article
- Direct-Acting Antivirals and Host-Targeting Approaches against Enterovirus B Infections: Recent Advances.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Structure and inhibition of SARS-CoV-1 and SARS-CoV-2 main proteases by oral antiviral compound AG7404.Antiviral research · 2022Article
- Targeting intercellular adhesion molecule-1 (ICAM-1) to reduce rhinovirus-induced acute exacerbations in chronic respiratory diseases.Inflammopharmacology · 2022Review
10 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
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
(E)-(S)-4-((S)-2-{3-[(5-methyl-isoxazole-3-carbonyl)-amino]-2-oxo-2H-pyridin-1-yl}-pent-4-ynoylamino)-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester (Compound 1) is a novel, irreversible inhibitor of human rhinovirus (HRV) 3C protease {inactivation rate constant (Kobs/[I]) of 223,000 M-1s-1}. In cell-based assays, Compound 1 was active against all HRV serotypes (35 of 35), HRV clinical isolates (5 of 5), and related picornaviruses (8 of 8) tested with mean 50% effective concentration (EC50) values of 50 nM (range, 14 to 122 nM), 77 nM (range, 72 to 89 nM), and 75 nM (range, 7 to 249 nM), respectively. Compound 1 inhibited HRV 3C-mediated polyprotein processing in infected cells in a concentration-dependent manner, providing direct confirmation that the cell-based antiviral activity is due to inhibition of 3C protease. In vitro and in vivo nonclinical safety studies showed Compound 1 to be without adverse effects at maximum achievable doses. Single oral doses of Compound 1 up to 2,000 mg in healthy volunteers were found to be safe and well tolerated in a phase I-ascending, single-dose study. Compound 1 estimated free observed maximum concentration in plasma (Cmax) for 500-, 1,000-, and 2,000-mg doses were higher than the protein binding-corrected EC50 required to inhibit 80% of the HRV serotypes tested. Treatment of HRV 52-infected cells with one to five 2-h pulses of 150 nM Compound 1 (corresponding to the Cmax at the 500-mg dose) was sufficient to effect a significant reduction in viral replication. These experiments highlight Compound 1 as a potent, orally bioavailable, irreversible inhibitor of HRV 3C protease and provide data that suggest that Cmax rather than the Cmin might be the key variable predicting clinical efficacy.
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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.