ArticleAntimicrobial agents and chemotherapy2009
Cyclosporine inhibits flavivirus replication through blocking the interaction between host cyclophilins and viral NS5 protein.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 132 citations in OpenAlex.
- Independent proviral and antiviral host factors recognize the same capsid protein in divergent human herpesviruses.PLoS pathogens · 2026Article
- Sulfonyl Anthranilic Acid Analogues Display Pan-Serotype Anti-Dengue Activity by Downregulating the Expression of Ribosomal Proteins Encoded by 5'-Terminal Oligopyrimidine Motif-Containing mRNA.Journal of medicinal chemistry · 2026Article
- Pharmaceutical Strategies for West Nile Virus in Europe, an Underrecognized Cause of Severe Disease and Mortality in Older Adults: From Supportive Care to Antiviral Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- West Nile Virus: Epidemiology, Surveillance, and Prophylaxis with a Comparative Insight from Italy and Iran.Vaccines · 2026Review
- All-atom molecular dynamics simulation of Cyclophilin A in complex with Sanglifehrin A.PloS one · 2026Article
- Host centric drug repurposing for viral diseases.PLoS computational biology · 2025Article
- Functional Roles and Host Interactions ofPathogens (Basel, Switzerland) · 2025Review
- Macrocycle-based PROTACs selectively degrade cyclophilin A and inhibit HIV-1 and HCV.Nature communications · 2025Article
- West Nile virus - a re-emerging global threat: recent advances in vaccines and drug discovery.Frontiers in cellular and infection microbiology · 2025Review
- i-DENV: development of QSAR based regression models for predicting inhibitors targeting non-structural (NS) proteins of dengue virus.Frontiers in pharmacology · 2025Article
- Pilot proteomic analysis of immune dysregulation in dengue with prior SARS-CoV-2 infection.Frontiers in immunology · 2025Observational
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- A Scoping Review of Arthropod-Borne Flavivirus Infections in Solid Organ Transplant Recipients.Transplant infectious disease : an official journal of the Transplantation Society · 2024Article
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- LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities.PLoS pathogens · 2023Article
- Review
- Antiviral effects of the fused tricyclic derivatives of indoline and imidazolidinone on ZIKV infection and RdRp activities of ZIKV and DENV.Virus research · 2023Article
- Non-Immunosuppressive Cyclophilin Inhibitors.Angewandte Chemie (International ed. in English) · 2022Review
- Contemporary exploitation of natural products for arthropod-borne pathogen transmission-blocking interventions.Parasites & vectors · 2022Review
- The Cyclophilin-Dependent Calcineurin Inhibitor Voclosporin Inhibits SARS-CoV-2 Replication in Cell Culture.Transplant international : official journal of the European Society for Organ Transplantation · 2022Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Although flaviviruses cause significant human diseases, no effective therapy is currently available. Host factors essential for viral replication are potential targets for antiviral development. Here we report that cyclophilins (CyPs), a family of cellular peptidyl-prolyl isomerases (PPIases), play a role in flavivirus replication. Huh-7.5 cells with knockdown of different isoforms of CyP were less efficient than parental cells in supporting flavivirus replication, including West Nile virus (WNV), dengue virus, and yellow fever virus. The low viral replication in CyP A (CyPA) knockdown cells could be rescued by trans supplying of a wild-type CyPA but not by trans supplying of a mutant CyPA (defective in the PPIase activity), indicating that the isomerase activity of CyPA is critical for viral replication. Immunoprecipitation and biochemical pulldown analyses showed that CyPA interacts with WNV genomic RNA and viral NS5 protein in the replication complex. Furthermore, antiviral experiments demonstrated that cyclosporine (Cs; an 11-amino-acid cyclic peptide known to block the PPIase activity of CyPA) inhibits flavivirus replication in cell culture at nontoxic concentrations. Time-of-addition and transient replicon results indicated that Cs inhibits flavivirus at the step of viral RNA synthesis. Biochemical analysis showed that Cs directly blocks the interaction between CyPA and WNV NS5 protein. Our results suggest that host CyPA is a component of flavivirus replication complex and could be targeted for potential antiviral development.
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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.