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

Autor: de Wilde AH; Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: A.H.de_Wilde@lumc.nl., Falzarano D; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, USA., Zevenhoven-Dobbe JC; Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands., Beugeling C; Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands., Fett C; Department of Microbiology, University of Iowa, Iowa City, USA., Martellaro C; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, USA., Posthuma CC; Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands., Feldmann H; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, USA., Perlman S; Department of Microbiology, University of Iowa, Iowa City, USA., Snijder EJ; Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: E.J.Snijder@lumc.nl.
Jazyk: angličtina
Zdroj: Virus research [Virus Res] 2017 Jan 15; Vol. 228, pp. 7-13. Date of Electronic Publication: 2016 Nov 10.
DOI: 10.1016/j.virusres.2016.11.011
Abstrakt: 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.
(Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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