title: Cyclosporin A inhibits the replication of diverse coronaviruses.
abstract: Low micromolar, non-cytotoxic concentrations of cyclosporin A (CsA) strongly affected the replication of severe acute respiratory syndrome coronavirus (SARS-CoV), human coronavirus 229E and mouse hepatitis virus in cell culture, as was evident from the strong inhibition of GFP reporter gene expression and a reduction of up to 4 logs in progeny titres. Upon high-multiplicity infection, CsA treatment rendered SARS-CoV RNA and protein synthesis almost undetectable, suggesting an early block in replication. siRNA-mediated knockdown of the expression of the prominent CsA targets cyclophilin A and B did not affect SARS-CoV replication, suggesting either that these specific cyclophilin family members are dispensable or that the reduced expression levels suffice to support replication.
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Adriaan H
authors.initials: AH
authors.lastname: de Wilde
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jessika C
authors.initials: JC
authors.lastname: Zevenhoven-Dobbe
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: van der Meer
authors.affiliation: Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.|Institute of Immunobiology, Kantonal Hospital St Gallen, St Gallen, Switzerland.
authors.forename: Volker
authors.initials: V
authors.lastname: Thiel
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Narayanan
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Shinji
authors.initials: S
authors.lastname: Makino
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Snijder
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: van Hemert
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D028941:Coronavirus 229E, Human / Q000187:drug effects* / Q000254:growth & development; D016572:Cyclosporine / Q000494:pharmacology*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006517:Murine hepatitis virus / Q000187:drug effects* / Q000254:growth & development; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000254:growth & development; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D049452:Green Fluorescent Proteins; D016572:Cyclosporine