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

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...

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Autores principales: de Wilde, Adriaan H., Falzarano, Darryl, Zevenhoven-Dobbe, Jessika C., Beugeling, Corrine, Fett, Craig, Martellaro, Cynthia, Posthuma, Clara C., Feldmann, Heinz, Perlman, Stanley, Snijder, Eric J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Authors. Published by Elsevier B.V. 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114565/
https://www.ncbi.nlm.nih.gov/pubmed/27840112
http://dx.doi.org/10.1016/j.virusres.2016.11.011
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author de Wilde, Adriaan H.
Falzarano, Darryl
Zevenhoven-Dobbe, Jessika C.
Beugeling, Corrine
Fett, Craig
Martellaro, Cynthia
Posthuma, Clara C.
Feldmann, Heinz
Perlman, Stanley
Snijder, Eric J.
author_facet de Wilde, Adriaan H.
Falzarano, Darryl
Zevenhoven-Dobbe, Jessika C.
Beugeling, Corrine
Fett, Craig
Martellaro, Cynthia
Posthuma, Clara C.
Feldmann, Heinz
Perlman, Stanley
Snijder, Eric J.
author_sort de Wilde, Adriaan H.
collection PubMed
description 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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spelling pubmed-71145652020-04-02 Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model de Wilde, Adriaan H. Falzarano, Darryl Zevenhoven-Dobbe, Jessika C. Beugeling, Corrine Fett, Craig Martellaro, Cynthia Posthuma, Clara C. Feldmann, Heinz Perlman, Stanley Snijder, Eric J. Virus Res Article 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. The Authors. Published by Elsevier B.V. 2017-01-15 2016-11-10 /pmc/articles/PMC7114565/ /pubmed/27840112 http://dx.doi.org/10.1016/j.virusres.2016.11.011 Text en © 2016 The Authors Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
de Wilde, Adriaan H.
Falzarano, Darryl
Zevenhoven-Dobbe, Jessika C.
Beugeling, Corrine
Fett, Craig
Martellaro, Cynthia
Posthuma, Clara C.
Feldmann, Heinz
Perlman, Stanley
Snijder, Eric J.
Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model
title Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model
title_full Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model
title_fullStr Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model
title_full_unstemmed Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model
title_short Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model
title_sort alisporivir inhibits mers- and sars-coronavirus replication in cell culture, but not sars-coronavirus infection in a mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114565/
https://www.ncbi.nlm.nih.gov/pubmed/27840112
http://dx.doi.org/10.1016/j.virusres.2016.11.011
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