ArticleThe Journal of biological chemistry2009
The isomerase active site of cyclophilin A is critical for hepatitis C virus replication.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
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
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 194 citations in OpenAlex.
- Broad-Spectrum Antiviral Activity of Cyclophilin Inhibitors Against Coronaviruses: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Independent proviral and antiviral host factors recognize the same capsid protein in divergent human herpesviruses.PLoS pathogens · 2026Article
- Cyclophilin A stabilizes the capsid protein p72 to facilitate African swine fever virus replication.Nature communications · 2026Article
- Human Cyclophilins-An Emerging Class of Drug Targets.Medicinal research reviews · 2026Review
- Overview of host-directed antiviral targets for future research and drug development.Acta pharmaceutica Sinica. B · 2025Review
- Cyclophilin A: promising target in cancer therapy.Cancer biology & therapy · 2024Review
- Article
- Cyclosporin A-Based PROTACs Can Deplete Abundant Cellular Cyclophilin A without Suppressing T Cell Activation.Molecules (Basel, Switzerland) · 2024Article
- Unraveling the dynamics of hepatitis C virus adaptive mutations and their impact on antiviral responses in primary human hepatocytes.Journal of virology · 2024Article
- Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers.Molecules (Basel, Switzerland) · 2024Review
- Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins.iScience · 2023Article
- The Cyclophilin Inhibitor Rencofilstat Decreases HCV-Induced Hepatocellular Carcinoma Independently of Its Antiviral Activity.Viruses · 2023Article
- Neutralization and receptor use of infectious culture-derived rat hepacivirus as a model for HCV.Hepatology (Baltimore, Md.) · 2022Article
- Repurposing of cyclophilin A inhibitors as broad-spectrum antiviral agents.Drug discovery today · 2022Review
- MxB Disrupts Hepatitis C Virus NS5A-CypA Complex: Insights From a Combined Theoretical and Experimental Approach.Frontiers in microbiology · 2022Article
- Emerging Roles of Cyclophilin A in Regulating Viral Cloaking.Frontiers in microbiology · 2022Review
- Cyclophilins and Their Roles in Hepatitis C Virus and Flavivirus Infections: Perspectives for Novel Antiviral Approaches.Pathogens (Basel, Switzerland) · 2021Review
- Cyclophilin A Inhibits Human Respiratory Syncytial Virus (RSV) Replication by Binding to RSV-N through Its PPIase Activity.Journal of virology · 2021Article
- Cyclosporin A: A Repurposable Drug in the Treatment of COVID-19?Frontiers in medicine · 2021Review
- Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery.Frontiers in pharmacology · 2021Review
53 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
9 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclosporine A and nonimmunosuppressive cyclophilin (Cyp) inhibitors such as Debio 025, NIM811, and SCY-635 block hepatitis C virus (HCV) replication in vitro. This effect was recently confirmed in HCV-infected patients where Debio 025 treatment dramatically decreased HCV viral load, suggesting that Cyps inhibitors represent a novel class of anti-HCV agents. However, it remains unclear how these compounds control HCV replication. Recent studies suggest that Cyps are important for HCV replication. However, a profound disagreement currently exists as to the respective roles of Cyp members in HCV replication. In this study, we analyzed the respective contribution of Cyp members to HCV replication by specifically knocking down their expression by both transient and stable small RNA interference. Only the CypA knockdown drastically decreased HCV replication. The re-expression of an exogenous CypA escape protein, which contains escape mutations at the small RNA interference recognition site, restored HCV replication, demonstrating the specificity for the CypA requirement. We then mutated residues that reside in the hydrophobic pocket of CypA where proline-containing peptide substrates and cyclosporine A bind and that are vital for the enzymatic or the hydrophobic pocket binding activity of CypA. Remarkably, these CypA mutants fail to restore HCV replication, suggesting for the first time that HCV exploits either the isomerase or the chaperone activity of CypA to replicate in hepatocytes and that CypA is the principal mediator of the Cyp inhibitor anti-HCV activity. Moreover, we demonstrated that the HCV NS5B polymerase associates with CypA via its enzymatic pocket. The study of the roles of Cyps in HCV replication should lead to the identification of new targets for the development of alternate anti-HCV therapies.
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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.