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

被引：53

作者：

de Wilde, Adriaan H. ^{[1
]}

Falzarano, Darryl ^{[2
]}

Zevenhoven-Dobbe, Jessika C. ^{[1
]}

Beugeling, Corrine ^{[1
]}

Fett, Craig ^{[3
]}

Martellaro, Cynthia ^{[2
]}

Posthuma, Clara C. ^{[1
]}

Feldmann, Heinz ^{[2
]}

Perlman, Stanley ^{[3
]}

Snijder, Eric J. ^{[1
]}

机构：

[1] Leiden Univ, Dept Med Microbiol, Mol Virol Lab, Med Ctr, Leiden, Netherlands

[2] NIAID, NIH, Hamilton, MT USA

[3] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA

来源：

VIRUS RESEARCH | 2017年 / 228卷

关键词：

RESPIRATORY SYNDROME CORONAVIRUS; GENOTYPE; INFECTION; HEPATITIS-C; CYCLOSPORINE-A; IN-VITRO; CYCLOPHILIN INHIBITORS; VIRUS; RIBAVIRIN; INTERFERON; COMBINATION;

D O I：

10.1016/j.virusres.2016.11.011

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

引用

页码：7 / 13

页数：7

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