title: Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model.
abstract: Currently, there is no registered treatment for infections with emerging zoonotic coronaviruses like SARS- and MERS-coronavirus. We here report that in cultured cells low-micromolar concentrations of alisporivir, a non-immunosuppressive cyclosporin A-analog, inhibit the replication of four different coronaviruses, including MERS- and SARS-coronavirus. Ribavirin was found to further potentiate the antiviral effect of alisporivir in these cell culture-based infection models, but this combination treatment was unable to improve the outcome of SARS-CoV infection in a mouse model. Nevertheless, our data provide a basis to further explore the potential of Cyp inhibitors as host-directed, broad-spectrum inhibitors of coronavirus replication.
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: A.H.de_Wilde@lumc.nl.
authors.forename: Adriaan H
authors.initials: AH
authors.lastname: de Wilde
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, USA.
authors.forename: Darryl
authors.initials: D
authors.lastname: Falzarano
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, 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, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Corrine
authors.initials: C
authors.lastname: Beugeling
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Fett
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Martellaro
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Clara C
authors.initials: CC
authors.lastname: Posthuma
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, USA.
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Perlman
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: E.J.Snijder@lumc.nl.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Snijder
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D018352:Coronavirus Infections / Q000188:drug therapy / Q000821:virology; D016572:Cyclosporine / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D065207:Middle East Respiratory Syndrome Coronavirus / Q000187:drug effects* / Q000502:physiology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000502:physiology*; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D016572:Cyclosporine; C499715:alisporivir