ArticleAntimicrobial agents and chemotherapy1999
In vitro antiviral activity of AG7088, a potent inhibitor of human rhinovirus 3C protease.
Article in Antimicrobial agents and chemotherapy, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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100 citing papers in PubMed, 223 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
- Phase II, randomized, double-blind, placebo-controlled studies of ruprintrivir nasal spray 2-percent suspension for prevention and treatment of experimentally induced rhinovirus colds in healthy volunteers.Antimicrobial agents and chemotherapy · 2003Trial
- Pharmacokinetics and safety of an antirhinoviral agent, ruprintrivir, in healthy volunteers.Antimicrobial agents and chemotherapy · 2002Trial
- A robust cell-based infection model for Rhinovirus C research and antiviral drug discovery.Npj viruses · 2026Article
- Genotype-by-inhibitor interactions to dissect enterovirus replication.Nature communications · 2026Article
- Comparative analysis of deep mutational scanning datasets in enteroviruses A and B identifies functional divergence and therapeutic targets.Nature ecology & evolution · 2026Article
- Structural insights into the antiviral efficacy of AG7404 against human rhinovirus 3C proteases.IUCrJ · 2026Article
- Development of enterovirus transencapsidation assays as tools to understand viral entry.The Journal of general virology · 2025Article
- Genotype-by-Inhibitor Interactions to Dissect Enterovirus Replication.Research square · 2025Article
- Comparative Analysis of Deep Mutational Scanning Datasets in Enteroviruses A and B Identifies Functional Divergence and Therapeutic Targets.Research square · 2025Article
- Advances in the Treatment of Enterovirus-D68 and Rhinovirus Respiratory Infections.Infectious disease reports · 2025Review
- Copper-catalyzed enantioselective three-component radical 1,4-perfluoroalkylamination of 1,3-dienes.Nature communications · 2025Article
- Gene Therapy with Enterovirus 3 C Protease: A Promising Strategy for Various Solid Tumors.Nature communications · 2025Article
- Enteroviral 3C protease cleaves N4BP1 to impair the host inflammatory response.Journal of virology · 2025Article
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- Antiviral Development for the Polio Endgame: Current Progress and Future Directions.Pathogens (Basel, Switzerland) · 2024Review
- Elucidating the Substrate Envelope of Enterovirus 68-3C Protease: Structural Basis of Specificity and Potential Resistance.Viruses · 2024Article
- Human norovirus cultivation systems and their use in antiviral research.Journal of virology · 2024Review
- Potent small molecule inhibitors against the 3C protease of foot-and-mouth disease virus.Microbiology spectrum · 2024Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AG7088 is a potent, irreversible inhibitor of human rhinovirus (HRV) 3C protease (inactivation rate constant (k(obs)/[I]) = 1,470,000 +/- 440,000 M(-1) s(-1) for HRV 14) that was discovered by protein structure-based drug design methodologies. In H1-HeLa and MRC-5 cell protection assays, AG7088 inhibited the replication of all HRV serotypes (48 of 48) tested with a mean 50% effective concentration (EC(50)) of 0.023 microM (range, 0.003 to 0.081 microM) and a mean EC(90) of 0.082 microM (range, 0.018 to 0.261 microM) as well as that of related picornaviruses including coxsackieviruses A21 and B3, enterovirus 70, and echovirus 11. No significant reductions in the antiviral activity of AG7088 were observed when assays were performed in the presence of alpha(1)-acid glycoprotein or mucin, proteins present in nasal secretions. The 50% cytotoxic concentration of AG7088 was >1,000 microM, yielding a therapeutic index of >12,346 to >333,333. In a single-cycle, time-of-addition assay, AG7088 demonstrated antiviral activity when added up to 6 h after infection. In contrast, a compound targeting viral attachment and/or uncoating was effective only when added at the initiation of virus infection. Direct inhibition of 3C proteolytic activity in infected cells treated with AG7088 was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of radiolabeled proteins, which showed a dose-dependent accumulation of viral precursor polyproteins and reduction of processed protein products. The broad spectrum of antiviral activity of AG7088, combined with its efficacy even when added late in the virus life cycle, highlights the advantages of 3C protease as a target and suggests that AG7088 will be a promising clinical candidate.
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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.