Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model
Identifieur interne : 000931 ( Pmc/Curation ); précédent : 000930; suivant : 000932Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model
Auteurs : Adriaan H. De Wilde [Pays-Bas] ; Darryl Falzarano [États-Unis] ; Jessika C. Zevenhoven-Dobbe [Pays-Bas] ; Corrine Beugeling [Pays-Bas] ; Craig Fett [États-Unis] ; Cynthia Martellaro [États-Unis] ; Clara C. Posthuma [Pays-Bas] ; Heinz Feldmann [États-Unis] ; Stanley Perlman [États-Unis] ; Eric J. Snijder [Pays-Bas]Source :
- Virus Research [ 0168-1702 ] ; 2016.
Abstract
In cell culture models, low-micromolar doses of alisporivir block SARS-CoV and MERS-CoV replication. Combination treatment with alisporivir and ribavirin increases the anti-MERS-CoV activity in cell culture. Combination treatment with alisporivir and ribavirin does not protect against SARS-CoV infection in a mouse model. Cyclophilin-binding drugs should be explored further in the context of host-directed anti-coronaviral strategies.
Url:
DOI: 10.1016/j.virusres.2016.11.011
PubMed: 27840112
PubMed Central: 7114565
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<front><div type="abstract" xml:lang="en"><title>Highlights</title>
<p><list list-type="simple" id="lis0005"><list-item id="lsti0005"><label>•</label>
<p id="par0005">In cell culture models, low-micromolar doses of alisporivir block SARS-CoV and MERS-CoV replication.</p>
</list-item>
<list-item id="lsti0010"><label>•</label>
<p id="par0010">Combination treatment with alisporivir and ribavirin increases the anti-MERS-CoV activity in cell culture.</p>
</list-item>
<list-item id="lsti0015"><label>•</label>
<p id="par0015">Combination treatment with alisporivir and ribavirin does not protect against SARS-CoV infection in a mouse model.</p>
</list-item>
<list-item id="lsti0020"><label>•</label>
<p id="par0020">Cyclophilin-binding drugs should be explored further in the context of host-directed anti-coronaviral strategies.</p>
</list-item>
</list>
</p>
</div>
</front>
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</TEI>
<pmc article-type="brief-report"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Virus Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Virus Res</journal-id>
<journal-title-group><journal-title>Virus Research</journal-title>
</journal-title-group>
<issn pub-type="ppub">0168-1702</issn>
<issn pub-type="epub">1872-7492</issn>
<publisher><publisher-name>The Authors. Published by Elsevier B.V.</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">27840112</article-id>
<article-id pub-id-type="pmc">7114565</article-id>
<article-id pub-id-type="publisher-id">S0168-1702(16)30552-4</article-id>
<article-id pub-id-type="doi">10.1016/j.virusres.2016.11.011</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" id="aut0005"><name><surname>de Wilde</surname>
<given-names>Adriaan H.</given-names>
</name>
<email>A.H.de_Wilde@lumc.nl</email>
<xref rid="aff0005" ref-type="aff">a</xref>
<xref rid="cor0005" ref-type="corresp">⁎</xref>
</contrib>
<contrib contrib-type="author" id="aut0010"><name><surname>Falzarano</surname>
<given-names>Darryl</given-names>
</name>
<xref rid="aff0010" ref-type="aff">b</xref>
<xref rid="fn0005" ref-type="fn">1</xref>
</contrib>
<contrib contrib-type="author" id="aut0015"><name><surname>Zevenhoven-Dobbe</surname>
<given-names>Jessika C.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author" id="aut0020"><name><surname>Beugeling</surname>
<given-names>Corrine</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author" id="aut0025"><name><surname>Fett</surname>
<given-names>Craig</given-names>
</name>
<xref rid="aff0015" ref-type="aff">c</xref>
</contrib>
<contrib contrib-type="author" id="aut0030"><name><surname>Martellaro</surname>
<given-names>Cynthia</given-names>
</name>
<xref rid="aff0010" ref-type="aff">b</xref>
</contrib>
<contrib contrib-type="author" id="aut0035"><name><surname>Posthuma</surname>
<given-names>Clara C.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author" id="aut0040"><name><surname>Feldmann</surname>
<given-names>Heinz</given-names>
</name>
<xref rid="aff0010" ref-type="aff">b</xref>
</contrib>
<contrib contrib-type="author" id="aut0045"><name><surname>Perlman</surname>
<given-names>Stanley</given-names>
</name>
<xref rid="aff0015" ref-type="aff">c</xref>
</contrib>
<contrib contrib-type="author" id="aut0050"><name><surname>Snijder</surname>
<given-names>Eric J.</given-names>
</name>
<email>E.J.Snijder@lumc.nl</email>
<xref rid="aff0005" ref-type="aff">a</xref>
<xref rid="cor0005" ref-type="corresp">⁎</xref>
</contrib>
</contrib-group>
<aff id="aff0005"><label>a</label>
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands</aff>
<aff id="aff0010"><label>b</label>
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, USA</aff>
<aff id="aff0015"><label>c</label>
Department of Microbiology, University of Iowa, Iowa City, USA</aff>
<author-notes><corresp id="cor0005"><label>⁎</label>
Corresponding authors. <email>A.H.de_Wilde@lumc.nl</email>
<email>E.J.Snijder@lumc.nl</email>
</corresp>
<fn id="fn0005"><label>1</label>
<p id="npar0030">Current address: Vaccine and Infectious Disease Organization - International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, Canada.</p>
</fn>
</author-notes>
<pub-date pub-type="pmc-release"><day>10</day>
<month>11</month>
<year>2016</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><day>15</day>
<month>1</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="epub"><day>10</day>
<month>11</month>
<year>2016</year>
</pub-date>
<volume>228</volume>
<fpage>7</fpage>
<lpage>13</lpage>
<history><date date-type="received"><day>1</day>
<month>9</month>
<year>2016</year>
</date>
<date date-type="rev-recd"><day>4</day>
<month>11</month>
<year>2016</year>
</date>
<date date-type="accepted"><day>7</day>
<month>11</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>© 2016 The Authors</copyright-statement>
<copyright-year>2016</copyright-year>
<license><license-p>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.</license-p>
</license>
</permissions>
<abstract abstract-type="author-highlights" id="abs0005"><title>Highlights</title>
<p><list list-type="simple" id="lis0005"><list-item id="lsti0005"><label>•</label>
<p id="par0005">In cell culture models, low-micromolar doses of alisporivir block SARS-CoV and MERS-CoV replication.</p>
</list-item>
<list-item id="lsti0010"><label>•</label>
<p id="par0010">Combination treatment with alisporivir and ribavirin increases the anti-MERS-CoV activity in cell culture.</p>
</list-item>
<list-item id="lsti0015"><label>•</label>
<p id="par0015">Combination treatment with alisporivir and ribavirin does not protect against SARS-CoV infection in a mouse model.</p>
</list-item>
<list-item id="lsti0020"><label>•</label>
<p id="par0020">Cyclophilin-binding drugs should be explored further in the context of host-directed anti-coronaviral strategies.</p>
</list-item>
</list>
</p>
</abstract>
<abstract id="abs0010"><p>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.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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