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

Adriaan H de Wilde; Darryl Falzarano; Jessika C Zevenhoven-Dobbe; Corrine Beugeling; Craig Fett; Cynthia Martellaro; Clara C Posthuma; Heinz Feldmann; Stanley Perlman; Eric J Snijder

doi:10.1016/j.virusres.2016.11.011

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. Epub 2016 Nov 10.

Affiliations

¹ Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: A.H.de_Wilde@lumc.nl.
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: E.J.Snijder@lumc.nl.

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.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents / pharmacology
Cell Line
Cells, Cultured
Coronavirus Infections / drug therapy
Coronavirus Infections / virology
Cyclosporine / pharmacology*
Cytopathogenic Effect, Viral / drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
Humans
Mice
Middle East Respiratory Syndrome Coronavirus / drug effects*
Middle East Respiratory Syndrome Coronavirus / physiology*
Severe Acute Respiratory Syndrome / drug therapy
Severe Acute Respiratory Syndrome / virology
Severe acute respiratory syndrome-related coronavirus / drug effects*
Severe acute respiratory syndrome-related coronavirus / physiology*
Virus Replication / drug effects*

Substances

Antiviral Agents
Cyclosporine
alisporivir