Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model

  • Virus Res. 2017 Jan 15;228:7-13. doi: 10.1016/j.virusres.2016.11.011.
Adriaan H de Wilde  1 ,  Darryl Falzarano  2 ,  Jessika C Zevenhoven-Dobbe  3 ,  Corrine Beugeling  3 ,  Craig Fett  4 ,  Cynthia Martellaro  2 ,  Clara C Posthuma  3 ,  Heinz Feldmann  2 ,  Stanley Perlman  4 ,  Eric J Snijder  5
Affiliations
  • 1. Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: [email protected].
  • 2. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, USA.
  • 3. Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
  • 4. Department of Microbiology, University of Iowa, Iowa City, USA.
  • 5. Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: [email protected].
PMID: 27840112 DOI: 10.1016/j.virusres.2016.11.011
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.

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