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

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

Journal article

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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 and Eric J Snijder

Virus research, Vol.228, pp.7-13

01/15/2017

DOI: 10.1016/j.virusres.2016.11.011

PMCID: PMC7114565

PMID: 27840112

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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.

Cell Line

Virus Replication - drug effects

Antiviral Agents - pharmacology

Cytopathogenic Effect, Viral - drug effects

Severe Acute Respiratory Syndrome - virology

Cyclosporine - pharmacology

Coronavirus Infections - drug therapy

Humans

Cells, Cultured

Middle East Respiratory Syndrome Coronavirus - drug effects

SARS Virus - drug effects

Severe Acute Respiratory Syndrome - drug therapy

Dose-Response Relationship, Drug

Animals

Coronavirus Infections - virology

Mice

SARS Virus - physiology

Middle East Respiratory Syndrome Coronavirus - physiology

Disease Models, Animal

Details

Title: Subtitle: Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model
Creators: Adriaan H de Wilde - Leiden University Medical Center
Darryl Falzarano - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, USA
Jessika C Zevenhoven-Dobbe - Leiden University Medical Center
Corrine Beugeling - Leiden University Medical Center
Craig Fett - Department of Microbiology, University of Iowa, Iowa City, USA
Cynthia Martellaro - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, USA
Clara C Posthuma - Leiden University Medical Center
Heinz Feldmann - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, USA
Stanley Perlman - Department of Microbiology, University of Iowa, Iowa City, USA
Eric J Snijder - Leiden University Medical Center
Resource Type: Journal article
Publication Details: Virus research, Vol.228, pp.7-13
DOI: 10.1016/j.virusres.2016.11.011
PMID: 27840112
PMCID: PMC7114565
NLM abbreviation: Virus Res
ISSN: 0168-1702
eISSN: 1872-7492
Publisher: Netherlands
Grant note: name: Council for Chemical Sciences (CW) of the Netherlands Organization for Scientific Research (NWO), award: 700.57.301
Language: English
Date published: 01/15/2017
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777355302771

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