CovidChloroV1, Main, Exploration, bibRecord, 000365

Ionophore antibiotic X-206 is a potent inhibitor of SARS-CoV-2 infection in vitro.

Identifieur interne : 000365 ( Main/Exploration ); précédent : 000364; suivant : 000366

Ionophore antibiotic X-206 is a potent inhibitor of SARS-CoV-2 infection in vitro.

Auteurs : Esben B. Svenningsen [Danemark] ; Jacob Thyrsted [Danemark] ; Julia Blay-Cadanet [Danemark] ; Han Liu [Danemark] ; Shaoquan Lin [Danemark] ; Jaime Moyano-Villameriel [Danemark] ; David Olagnier [Danemark] ; Manja Idorn [Danemark] ; S Ren R. Paludan [Danemark] ; Christian K. Holm [Danemark] ; Thomas B. Poulsen [Danemark]

Source :

Antiviral research [ 1872-9096 ] ; 2021.

RBID : pubmed:33248195

Descripteurs français

KwdFr :
- Animaux (MeSH), Antibactériens (pharmacologie), Antiviraux (pharmacologie), Cellules Vero (MeSH), Humains (MeSH), Ionophores (pharmacologie), Réplication virale (effets des médicaments et des substances chimiques), Éthers cycliques (pharmacologie).
MESH :
- effets des médicaments et des substances chimiques : Réplication virale.
- pharmacologie : Antibactériens, Antiviraux, Ionophores, Éthers cycliques.
- Animaux, Cellules Vero, Humains.

English descriptors

KwdEn :
- Animals (MeSH), Anti-Bacterial Agents (pharmacology), Antiviral Agents (pharmacology), COVID-19 (drug therapy), Chlorocebus aethiops (MeSH), Ethers, Cyclic (pharmacology), Humans (MeSH), Ionophores (pharmacology), SARS-CoV-2 (drug effects), Vero Cells (MeSH), Virus Replication (drug effects).
MESH :
- chemical , pharmacology : Anti-Bacterial Agents, Antiviral Agents, Ethers, Cyclic, Ionophores.
- drug effects : SARS-CoV-2, Virus Replication.
- drug therapy : COVID-19.
- Animals, Chlorocebus aethiops, Humans, Vero Cells.

Abstract

Pandemic spread of emerging human pathogenic viruses, such as the current SARS-CoV-2, poses both an immediate and future challenge to human health and society. Currently, effective treatment of infection with SARS-CoV-2 is limited and broad spectrum antiviral therapies to meet other emerging pandemics are absent leaving the World population largely unprotected. Here, we have identified distinct members of the family of polyether ionophore antibiotics with potent ability to inhibit SARS-CoV-2 replication and cytopathogenicity in cells. Several compounds from this class displayed more than 100-fold selectivity between viral-induced cytopathogenicity and inhibition of cell viability, however the compound X-206 displayed >500-fold selectivity and was furthermore able to inhibit viral replication even at sub-nM levels. The antiviral mechanism of the polyether ionophores is currently not understood in detail. We demonstrate, e.g. through unbiased bioactivity profiling, that their effects on the host cells differ from those of cationic amphiphiles such as hydroxychloroquine. Collectively, our data suggest that polyether ionophore antibiotics should be subject to further investigations as potential broad-spectrum antiviral agents.

DOI: 10.1016/j.antiviral.2020.104988
PubMed: 33248195
PubMed Central: PMC7687369

Affiliations:

Danemark

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000755
to stream Main, to step Curation: 000755

Le document en format XML

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<term>COVID-19 (drug therapy)</term>
<term>Chlorocebus aethiops (MeSH)</term>
<term>Ethers, Cyclic (pharmacology)</term>
<term>Humans (MeSH)</term>
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<term>Antibactériens (pharmacologie)</term>
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<term>Humains (MeSH)</term>
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<term>Éthers cycliques (pharmacologie)</term>
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<front><div type="abstract" xml:lang="en">Pandemic spread of emerging human pathogenic viruses, such as the current SARS-CoV-2, poses both an immediate and future challenge to human health and society. Currently, effective treatment of infection with SARS-CoV-2 is limited and broad spectrum antiviral therapies to meet other emerging pandemics are absent leaving the World population largely unprotected. Here, we have identified distinct members of the family of polyether ionophore antibiotics with potent ability to inhibit SARS-CoV-2 replication and cytopathogenicity in cells. Several compounds from this class displayed more than 100-fold selectivity between viral-induced cytopathogenicity and inhibition of cell viability, however the compound X-206 displayed >500-fold selectivity and was furthermore able to inhibit viral replication even at sub-nM levels. The antiviral mechanism of the polyether ionophores is currently not understood in detail. We demonstrate, e.g. through unbiased bioactivity profiling, that their effects on the host cells differ from those of cationic amphiphiles such as hydroxychloroquine. Collectively, our data suggest that polyether ionophore antibiotics should be subject to further investigations as potential broad-spectrum antiviral agents.</div>
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<Abstract><AbstractText>Pandemic spread of emerging human pathogenic viruses, such as the current SARS-CoV-2, poses both an immediate and future challenge to human health and society. Currently, effective treatment of infection with SARS-CoV-2 is limited and broad spectrum antiviral therapies to meet other emerging pandemics are absent leaving the World population largely unprotected. Here, we have identified distinct members of the family of polyether ionophore antibiotics with potent ability to inhibit SARS-CoV-2 replication and cytopathogenicity in cells. Several compounds from this class displayed more than 100-fold selectivity between viral-induced cytopathogenicity and inhibition of cell viability, however the compound X-206 displayed >500-fold selectivity and was furthermore able to inhibit viral replication even at sub-nM levels. The antiviral mechanism of the polyether ionophores is currently not understood in detail. We demonstrate, e.g. through unbiased bioactivity profiling, that their effects on the host cells differ from those of cationic amphiphiles such as hydroxychloroquine. Collectively, our data suggest that polyether ionophore antibiotics should be subject to further investigations as potential broad-spectrum antiviral agents.</AbstractText>
<CopyrightInformation>Copyright © 2020 Elsevier B.V. All rights reserved.</CopyrightInformation>
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<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Svenningsen</LastName>
<ForeName>Esben B</ForeName>
<Initials>EB</Initials>
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<Initials>J</Initials>
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</AffiliationInfo>
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<Initials>H</Initials>
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</AffiliationInfo>
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<ForeName>Manja</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000, Aarhus C, Denmark.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Paludan</LastName>
<ForeName>Søren R</ForeName>
<Initials>SR</Initials>
<AffiliationInfo><Affiliation>Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000, Aarhus C, Denmark.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Holm</LastName>
<ForeName>Christian K</ForeName>
<Initials>CK</Initials>
<AffiliationInfo><Affiliation>Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000, Aarhus C, Denmark. Electronic address: holm@biomed.au.dk.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Poulsen</LastName>
<ForeName>Thomas B</ForeName>
<Initials>TB</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry, Aarhus University, Langelandsgade 140, DK-8000, Aarhus C, Denmark. Electronic address: thpou@chem.au.dk.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2020</Year>
<Month>11</Month>
<Day>25</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>Netherlands</Country>
<MedlineTA>Antiviral Res</MedlineTA>
<NlmUniqueID>8109699</NlmUniqueID>
<ISSNLinking>0166-3542</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000900">Anti-Bacterial Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D004988">Ethers, Cyclic</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007476">Ionophores</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C437367">X-206, polyether antibiotic</NameOfSubstance>
</Chemical>
</ChemicalList>
<SupplMeshList><SupplMeshName Type="Protocol" UI="C000705127">COVID-19 drug treatment</SupplMeshName>
</SupplMeshList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000900" MajorTopicYN="N">Anti-Bacterial Agents</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004988" MajorTopicYN="N">Ethers, Cyclic</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007476" MajorTopicYN="N">Ionophores</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014709" MajorTopicYN="N">Vero Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014779" MajorTopicYN="N">Virus Replication</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Antiviral agent</Keyword>
<Keyword MajorTopicYN="Y">Coronavirus</Keyword>
<Keyword MajorTopicYN="Y">Polyether ionophore</Keyword>
<Keyword MajorTopicYN="Y">SARS-CoV-2</Keyword>
<Keyword MajorTopicYN="Y">X-206</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year>
<Month>07</Month>
<Day>22</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2020</Year>
<Month>11</Month>
<Day>04</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2020</Year>
<Month>11</Month>
<Day>18</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2020</Year>
<Month>11</Month>
<Day>29</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2021</Year>
<Month>1</Month>
<Day>16</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2020</Year>
<Month>11</Month>
<Day>28</Day>
<Hour>20</Hour>
<Minute>7</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">33248195</ArticleId>
<ArticleId IdType="pii">S0166-3542(20)30402-2</ArticleId>
<ArticleId IdType="doi">10.1016/j.antiviral.2020.104988</ArticleId>
<ArticleId IdType="pmc">PMC7687369</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Danemark</li>
</country>
</list>
<tree><country name="Danemark"><noRegion><name sortKey="Svenningsen, Esben B" sort="Svenningsen, Esben B" uniqKey="Svenningsen E" first="Esben B" last="Svenningsen">Esben B. Svenningsen</name>
</noRegion>
<name sortKey="Blay Cadanet, Julia" sort="Blay Cadanet, Julia" uniqKey="Blay Cadanet J" first="Julia" last="Blay-Cadanet">Julia Blay-Cadanet</name>
<name sortKey="Holm, Christian K" sort="Holm, Christian K" uniqKey="Holm C" first="Christian K" last="Holm">Christian K. Holm</name>
<name sortKey="Idorn, Manja" sort="Idorn, Manja" uniqKey="Idorn M" first="Manja" last="Idorn">Manja Idorn</name>
<name sortKey="Lin, Shaoquan" sort="Lin, Shaoquan" uniqKey="Lin S" first="Shaoquan" last="Lin">Shaoquan Lin</name>
<name sortKey="Liu, Han" sort="Liu, Han" uniqKey="Liu H" first="Han" last="Liu">Han Liu</name>
<name sortKey="Moyano Villameriel, Jaime" sort="Moyano Villameriel, Jaime" uniqKey="Moyano Villameriel J" first="Jaime" last="Moyano-Villameriel">Jaime Moyano-Villameriel</name>
<name sortKey="Olagnier, David" sort="Olagnier, David" uniqKey="Olagnier D" first="David" last="Olagnier">David Olagnier</name>
<name sortKey="Paludan, S Ren R" sort="Paludan, S Ren R" uniqKey="Paludan S" first="S Ren R" last="Paludan">S Ren R. Paludan</name>
<name sortKey="Poulsen, Thomas B" sort="Poulsen, Thomas B" uniqKey="Poulsen T" first="Thomas B" last="Poulsen">Thomas B. Poulsen</name>
<name sortKey="Thyrsted, Jacob" sort="Thyrsted, Jacob" uniqKey="Thyrsted J" first="Jacob" last="Thyrsted">Jacob Thyrsted</name>
</country>
</tree>
</affiliations>
</record>

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	Serveur d'exploration COVID et hydrochloroquine
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Serveur d'exploration COVID et hydrochloroquine

Ionophore antibiotic X-206 is a potent inhibitor of SARS-CoV-2 infection in vitro.

Ionophore antibiotic X-206 is a potent inhibitor of SARS-CoV-2 infection in vitro.

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