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Human coronavirus NL63 replication is cyclophilin A-dependent and inhibited by non-immunosuppressive cyclosporine A-derivatives including Alisporivir.

Identifieur interne : 000F89 ( PubMed/Checkpoint ); précédent : 000F88; suivant : 000F90

Human coronavirus NL63 replication is cyclophilin A-dependent and inhibited by non-immunosuppressive cyclosporine A-derivatives including Alisporivir.

Auteurs : Javier Carbajo-Lozoya [Allemagne] ; Yue Ma-Lauer [Allemagne] ; Miroslav Maleševi [Allemagne] ; Martin Theuerkorn [Allemagne] ; Viktoria Kahlert [Allemagne] ; Erik Prell [Allemagne] ; Brigitte Von Brunn [Allemagne] ; Doreen Muth [Allemagne] ; Thomas F. Baumert [France] ; Christian Drosten [Allemagne] ; Gunter Fischer [Allemagne] ; Albrecht Von Brunn [Allemagne]

Source :

RBID : pubmed:24566223

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English descriptors

Abstract

Until recently, there were no effective drugs available blocking coronavirus (CoV) infection in humans and animals. We have shown before that CsA and FK506 inhibit coronavirus replication (Carbajo-Lozoya, J., Müller, M.A., Kallies, S., Thiel, V., Drosten, C., von Brunn, A. Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506. Virus Res. 2012; Pfefferle, S., Schöpf, J., Kögl, M., Friedel, C., Müller, M.A., Stellberger, T., von Dall'Armi, E., Herzog, P., Kallies, S., Niemeyer, D., Ditt, V., Kuri, T., Züst, R., Schwarz, F., Zimmer, R., Steffen, I., Weber, F., Thiel, V., Herrler, G., Thiel, H.-J., Schwegmann-Weßels, C., Pöhlmann, S., Haas, J., Drosten, C. and von Brunn, A. The SARS-Coronavirus-host interactome: identification of cyclophilins as target for pan-Coronavirus inhibitors. PLoS Pathog., 2011). Here we demonstrate that CsD Alisporivir, NIM811 as well as novel non-immunosuppressive derivatives of CsA and FK506 strongly inhibit the growth of human coronavirus HCoV-NL63 at low micromolar, non-cytotoxic concentrations in cell culture. We show by qPCR analysis that virus replication is diminished up to four orders of magnitude to background levels. Knockdown of the cellular Cyclophilin A (CypA/PPIA) gene in Caco-2 cells prevents replication of HCoV-NL63, suggesting that CypA is required for virus replication. Collectively, our results uncover Cyclophilin A as a host target for CoV infection and provide new strategies for urgently needed therapeutic approaches.

DOI: 10.1016/j.virusres.2014.02.010
PubMed: 24566223


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Le document en format XML

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<name sortKey="Kahlert, Viktoria" sort="Kahlert, Viktoria" uniqKey="Kahlert V" first="Viktoria" last="Kahlert">Viktoria Kahlert</name>
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<name sortKey="Prell, Erik" sort="Prell, Erik" uniqKey="Prell E" first="Erik" last="Prell">Erik Prell</name>
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<name sortKey="Von Brunn, Brigitte" sort="Von Brunn, Brigitte" uniqKey="Von Brunn B" first="Brigitte" last="Von Brunn">Brigitte Von Brunn</name>
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<name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
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<name sortKey="Fischer, Gunter" sort="Fischer, Gunter" uniqKey="Fischer G" first="Gunter" last="Fischer">Gunter Fischer</name>
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<name sortKey="Von Brunn, Albrecht" sort="Von Brunn, Albrecht" uniqKey="Von Brunn A" first="Albrecht" last="Von Brunn">Albrecht Von Brunn</name>
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<term>Antiviral Agents (pharmacology)</term>
<term>Caco-2 Cells</term>
<term>Coronavirus NL63, Human (drug effects)</term>
<term>Coronavirus NL63, Human (physiology)</term>
<term>Cyclophilin A (metabolism)</term>
<term>Cyclosporine (pharmacology)</term>
<term>Humans</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Tacrolimus (pharmacology)</term>
<term>Virus Replication (drug effects)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Antiviraux (pharmacologie)</term>
<term>Cellules Caco-2</term>
<term>Ciclosporine (pharmacologie)</term>
<term>Coronavirus humain NL63 ()</term>
<term>Coronavirus humain NL63 (physiologie)</term>
<term>Cyclophiline A (métabolisme)</term>
<term>Humains</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Réplication virale ()</term>
<term>Tacrolimus (pharmacologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Cyclophilin A</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Antiviral Agents</term>
<term>Cyclosporine</term>
<term>Tacrolimus</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Coronavirus NL63, Human</term>
<term>Virus Replication</term>
</keywords>
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<term>Cyclophiline A</term>
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<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr">
<term>Antiviraux</term>
<term>Ciclosporine</term>
<term>Tacrolimus</term>
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<term>Coronavirus humain NL63</term>
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<term>Coronavirus NL63, Human</term>
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<term>Caco-2 Cells</term>
<term>Humans</term>
<term>Real-Time Polymerase Chain Reaction</term>
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<term>Cellules Caco-2</term>
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<term>Réaction de polymérisation en chaine en temps réel</term>
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<div type="abstract" xml:lang="en">Until recently, there were no effective drugs available blocking coronavirus (CoV) infection in humans and animals. We have shown before that CsA and FK506 inhibit coronavirus replication (Carbajo-Lozoya, J., Müller, M.A., Kallies, S., Thiel, V., Drosten, C., von Brunn, A. Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506. Virus Res. 2012; Pfefferle, S., Schöpf, J., Kögl, M., Friedel, C., Müller, M.A., Stellberger, T., von Dall'Armi, E., Herzog, P., Kallies, S., Niemeyer, D., Ditt, V., Kuri, T., Züst, R., Schwarz, F., Zimmer, R., Steffen, I., Weber, F., Thiel, V., Herrler, G., Thiel, H.-J., Schwegmann-Weßels, C., Pöhlmann, S., Haas, J., Drosten, C. and von Brunn, A. The SARS-Coronavirus-host interactome: identification of cyclophilins as target for pan-Coronavirus inhibitors. PLoS Pathog., 2011). Here we demonstrate that CsD Alisporivir, NIM811 as well as novel non-immunosuppressive derivatives of CsA and FK506 strongly inhibit the growth of human coronavirus HCoV-NL63 at low micromolar, non-cytotoxic concentrations in cell culture. We show by qPCR analysis that virus replication is diminished up to four orders of magnitude to background levels. Knockdown of the cellular Cyclophilin A (CypA/PPIA) gene in Caco-2 cells prevents replication of HCoV-NL63, suggesting that CypA is required for virus replication. Collectively, our results uncover Cyclophilin A as a host target for CoV infection and provide new strategies for urgently needed therapeutic approaches. </div>
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<DateCompleted>
<Year>2014</Year>
<Month>12</Month>
<Day>01</Day>
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<DateRevised>
<Year>2020</Year>
<Month>04</Month>
<Day>07</Day>
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<ISSN IssnType="Electronic">1872-7492</ISSN>
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<Volume>184</Volume>
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<Year>2014</Year>
<Month>May</Month>
<Day>12</Day>
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</JournalIssue>
<Title>Virus research</Title>
<ISOAbbreviation>Virus Res.</ISOAbbreviation>
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<ArticleTitle>Human coronavirus NL63 replication is cyclophilin A-dependent and inhibited by non-immunosuppressive cyclosporine A-derivatives including Alisporivir.</ArticleTitle>
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<Abstract>
<AbstractText>Until recently, there were no effective drugs available blocking coronavirus (CoV) infection in humans and animals. We have shown before that CsA and FK506 inhibit coronavirus replication (Carbajo-Lozoya, J., Müller, M.A., Kallies, S., Thiel, V., Drosten, C., von Brunn, A. Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506. Virus Res. 2012; Pfefferle, S., Schöpf, J., Kögl, M., Friedel, C., Müller, M.A., Stellberger, T., von Dall'Armi, E., Herzog, P., Kallies, S., Niemeyer, D., Ditt, V., Kuri, T., Züst, R., Schwarz, F., Zimmer, R., Steffen, I., Weber, F., Thiel, V., Herrler, G., Thiel, H.-J., Schwegmann-Weßels, C., Pöhlmann, S., Haas, J., Drosten, C. and von Brunn, A. The SARS-Coronavirus-host interactome: identification of cyclophilins as target for pan-Coronavirus inhibitors. PLoS Pathog., 2011). Here we demonstrate that CsD Alisporivir, NIM811 as well as novel non-immunosuppressive derivatives of CsA and FK506 strongly inhibit the growth of human coronavirus HCoV-NL63 at low micromolar, non-cytotoxic concentrations in cell culture. We show by qPCR analysis that virus replication is diminished up to four orders of magnitude to background levels. Knockdown of the cellular Cyclophilin A (CypA/PPIA) gene in Caco-2 cells prevents replication of HCoV-NL63, suggesting that CypA is required for virus replication. Collectively, our results uncover Cyclophilin A as a host target for CoV infection and provide new strategies for urgently needed therapeutic approaches. </AbstractText>
<CopyrightInformation>Copyright © 2014 Elsevier B.V. All rights reserved.</CopyrightInformation>
</Abstract>
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<LastName>Carbajo-Lozoya</LastName>
<ForeName>Javier</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Max-von-Pettenkofer Institut, Ludwig-Maximilians-Universität, München, Germany.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Ma-Lauer</LastName>
<ForeName>Yue</ForeName>
<Initials>Y</Initials>
<AffiliationInfo>
<Affiliation>Max-von-Pettenkofer Institut, Ludwig-Maximilians-Universität, München, Germany.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Malešević</LastName>
<ForeName>Miroslav</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Martin-Luther-Universität Halle-Wittenberg, Institute of Biochemistry and Biotechnology, Division of Enzymology, Halle, Germany.</Affiliation>
</AffiliationInfo>
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<LastName>Theuerkorn</LastName>
<ForeName>Martin</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Max-Planck-Institute of Biophysical Chemistry Göttingen, BO Halle (Saale), Germany.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Kahlert</LastName>
<ForeName>Viktoria</ForeName>
<Initials>V</Initials>
<AffiliationInfo>
<Affiliation>Max-Planck-Institute of Biophysical Chemistry Göttingen, BO Halle (Saale), Germany.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Prell</LastName>
<ForeName>Erik</ForeName>
<Initials>E</Initials>
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<LastName>von Brunn</LastName>
<ForeName>Brigitte</ForeName>
<Initials>B</Initials>
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<LastName>Muth</LastName>
<ForeName>Doreen</ForeName>
<Initials>D</Initials>
<AffiliationInfo>
<Affiliation>Institut für Virologie, Universität Bonn, Bonn, Germany.</Affiliation>
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<LastName>Baumert</LastName>
<ForeName>Thomas F</ForeName>
<Initials>TF</Initials>
<AffiliationInfo>
<Affiliation>Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg, Strasbourg, France.</Affiliation>
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<LastName>Drosten</LastName>
<ForeName>Christian</ForeName>
<Initials>C</Initials>
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<Affiliation>Institut für Virologie, Universität Bonn, Bonn, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Fischer</LastName>
<ForeName>Gunter</ForeName>
<Initials>G</Initials>
<AffiliationInfo>
<Affiliation>Max-Planck-Institute of Biophysical Chemistry Göttingen, BO Halle (Saale), Germany.</Affiliation>
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<LastName>von Brunn</LastName>
<ForeName>Albrecht</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Max-von-Pettenkofer Institut, Ludwig-Maximilians-Universität, München, Germany. Electronic address: vonbrunn@mvp.uni-muenchen.de.</Affiliation>
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<Year>2014</Year>
<Month>02</Month>
<Day>22</Day>
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<Country>Netherlands</Country>
<MedlineTA>Virus Res</MedlineTA>
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<MeshHeading>
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<Keyword MajorTopicYN="N">Cyclosporine/FK506-non-immunosuppressive derivatives</Keyword>
<Keyword MajorTopicYN="N">FKBP</Keyword>
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