ArticleAntimicrobial agents and chemotherapy2007
In vitro resistance study of rupintrivir, a novel inhibitor of human rhinovirus 3C protease.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed.
- Target-Based Antiviral Drug Development Against Human Respiratory Viruses.Pathogens (Basel, Switzerland) · 2026Review
- Establishment of an oral enterovirus 71 (EV71) infection model in immunocompetent mice for antiviral therapy evaluation.Journal of virology · 2026Article
- Infection-specific long-chain fatty acid metabolism as a broad anti-enterovirus target.bioRxiv : the preprint server for biology · 2026Article
- Structural insights into the antiviral efficacy of AG7404 against human rhinovirus 3C proteases.IUCrJ · 2026Article
- Broad-spectrum host-targeting antivirals for rhinovirus infections: mechanisms and future perspectives.Frontiers in immunology · 2026Review
- Article
- Discovery of non-covalent rhinovirus 3Cpro inhibitors by molecular docking,Frontiers in pharmacology · 2025Article
- Elucidating the Substrate Envelope of Enterovirus 68-3C Protease: Structural Basis of Specificity and Potential Resistance.Viruses · 2024Article
- Breaking the Chain: Protease Inhibitors as Game Changers in Respiratory Viruses Management.International journal of molecular sciences · 2024Review
- 4-Trifluoromethyl bithiazoles as broad-spectrum antimicrobial agents for virus-related bacterial infections or co-infections.RSC medicinal chemistry · 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
- Small Molecules Targeting 3C Protease Inhibit FMDV Replication and Exhibit Virucidal Effect in Cell-Based Assays.Viruses · 2023Article
- Accelerating antiviral drug discovery: lessons from COVID-19.Nature reviews. Drug discovery · 2023Review
- Andrographolide and Deoxyandrographolide Inhibit Protease and IFN-Antagonist Activities of Foot-and-Mouth Disease Virus 3CAnimals : an open access journal from MDPI · 2022Article
- Chemical Evolution of Rhinovirus Identifies Capsid-Destabilizing Mutations Driving Low-pH-Independent Genome Uncoating.Journal of virology · 2022Article
- RIPK1 Is Cleaved by 3C Protease of Rhinovirus A and B Strains and Minor and Major Groups.Viruses · 2021Article
- Inhibitors of Coronavirus 3CL Proteases Protect Cells from Protease-Mediated Cytotoxicity.Journal of virology · 2021Article
- α-Amidoaldehydes as Substrates in Rhodium-Catalyzed Intermolecular Alkyne Hydroacylation: The Synthesis of α-Amidoketones.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- [Rhinoviruses].Der Internist · 2019Review
- Rhinoviruses and Their Receptors.Chest · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rupintrivir (formerly AG7088) is an irreversible inhibitor of the human rhinovirus (HRV) 3C protease that has been demonstrated to have in vitro activity against all HRVs tested, consistent with its interaction with a strictly conserved subset of amino acids in the 3C protease. The potential for resistance was studied following in vitro serial passage of HRV serotypes 14, 2, 39, and Hanks in the presence of increasing rupintrivir concentrations. HRV variants with reduced susceptibilities to rupintrivir (sevenfold for HRV 14) or with no significant reductions in susceptibility but genotypic changes (HRV 2, 39, and Hanks) were initially isolated following 14 to 40 cumulative days in culture (three to six passages). Sequence analysis of the 3C protease identified one to three substitutions in diverse patterns but with common features (T129T/A, T131T/A, and T143P/S in HRV 14; N165T in HRV 2; N130N/K and L136L/F in HRV 39; T130A in HRV Hanks). Notably, three of the four HRV variants contained a substitution at residue 130 (residue 129 in HRV 14). Continued selection in the presence of escalating concentrations of rupintrivir (40 to 72 days) resulted in the accumulation of additional mutations (A121A/V and Y139Y/H in HRV 14, E3E/G and A103A/V in HRV 2, S105T in HRV 39), with only minimal further reductions in susceptibility (up to fivefold). The ability of specific substitutions to confer resistance was examined by susceptibility testing of HRV 14 variants constructed to contain 3C protease mutations. In summary, the slow accumulation of multiple amino acid substitutions with only minimal to moderate reductions in susceptibility highlight the advantages of 3C protease as an antiviral target.
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.