Amiodarone alters late endosomes and inhibits SARS coronavirus infection at a post-endosomal level.
Identifieur interne : 001B96 ( PubMed/Checkpoint ); précédent : 001B95; suivant : 001B97Amiodarone alters late endosomes and inhibits SARS coronavirus infection at a post-endosomal level.
Auteurs : Konrad Stadler [Italie] ; Huy Riem Ha ; Vincenzo Ciminale ; Carlo Spirli ; Giulietta Saletti ; Marco Schiavon ; Daniela Bruttomesso ; Laurent Bigler ; Ferenc Follath ; Andrea Pettenazzo ; Aldo BaritussioSource :
- American journal of respiratory cell and molecular biology [ 1535-4989 ] ; 2008.
Descripteurs français
- KwdFr :
- Amiodarone (pharmacocinétique), Amiodarone (pharmacologie), Animaux, Antiviraux (pharmacocinétique), Antiviraux (pharmacologie), Cathepsine L, Cathepsines (métabolisme), Cellules Vero, Cysteine endopeptidases (métabolisme), Cytoplasme (), Cytoplasme (métabolisme), Endosomes (), Endosomes (métabolisme), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (métabolisme), Humains, Isotopes de l'iode (), Macrophages alvéolaires (), Macrophages alvéolaires (métabolisme), Macrophages alvéolaires (virologie), Membrane cellulaire (), Membrane cellulaire (métabolisme), Protéines de l'enveloppe virale (métabolisme), Syndrome respiratoire aigu sévère (métabolisme), Syndrome respiratoire aigu sévère (traitement médicamenteux), Syndrome respiratoire aigu sévère (virologie), Vacuoles (), Vacuoles (métabolisme), Virus du SRAS (), Virus du SRAS (physiologie).
- MESH :
- métabolisme : Cathepsines, Cysteine endopeptidases, Cytoplasme, Endosomes, Glycoprotéines membranaires, Macrophages alvéolaires, Membrane cellulaire, Protéines de l'enveloppe virale, Syndrome respiratoire aigu sévère, Vacuoles.
- pharmacocinétique : Amiodarone, Antiviraux.
- pharmacologie : Amiodarone, Antiviraux.
- physiologie : Virus du SRAS.
- traitement médicamenteux : Syndrome respiratoire aigu sévère.
- virologie : Macrophages alvéolaires, Syndrome respiratoire aigu sévère.
- Animaux, Cathepsine L, Cellules Vero, Cytoplasme, Endosomes, Glycoprotéine de spicule des coronavirus, Humains, Isotopes de l'iode, Macrophages alvéolaires, Membrane cellulaire, Vacuoles, Virus du SRAS.
English descriptors
- KwdEn :
- Amiodarone (pharmacokinetics), Amiodarone (pharmacology), Animals, Antiviral Agents (pharmacokinetics), Antiviral Agents (pharmacology), Cathepsin L, Cathepsins (metabolism), Cell Membrane (drug effects), Cell Membrane (metabolism), Chlorocebus aethiops, Cysteine Endopeptidases (metabolism), Cytoplasm (drug effects), Cytoplasm (metabolism), Endosomes (drug effects), Endosomes (metabolism), Humans, Iodine Isotopes (chemistry), Macrophages, Alveolar (drug effects), Macrophages, Alveolar (metabolism), Macrophages, Alveolar (virology), Membrane Glycoproteins (metabolism), SARS Virus (drug effects), SARS Virus (physiology), Severe Acute Respiratory Syndrome (drug therapy), Severe Acute Respiratory Syndrome (metabolism), Severe Acute Respiratory Syndrome (virology), Spike Glycoprotein, Coronavirus, Vacuoles (drug effects), Vacuoles (metabolism), Vero Cells, Viral Envelope Proteins (metabolism).
- MESH :
- chemical , chemistry : Iodine Isotopes.
- chemical , metabolism : Cathepsins, Cysteine Endopeptidases, Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , pharmacokinetics : Amiodarone, Antiviral Agents.
- chemical , pharmacology : Amiodarone, Antiviral Agents.
- drug effects : Cell Membrane, Cytoplasm, Endosomes, Macrophages, Alveolar, SARS Virus, Vacuoles.
- drug therapy : Severe Acute Respiratory Syndrome.
- metabolism : Cell Membrane, Cytoplasm, Endosomes, Macrophages, Alveolar, Severe Acute Respiratory Syndrome, Vacuoles.
- physiology : SARS Virus.
- virology : Macrophages, Alveolar, Severe Acute Respiratory Syndrome.
- Animals, Cathepsin L, Chlorocebus aethiops, Humans, Spike Glycoprotein, Coronavirus, Vero Cells.
Abstract
Amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation of vacuoles, but uptake and intracellular distribution of the drug, origin of vacuoles, and functional consequences of amiodarone accumulation remain unclear. Our objective was to study amiodarone uptake, clarify the origin of vacuoles, and investigate the effect of amiodarone on the life cycle of the coronavirus responsible for the Severe Acute Respiratory Syndrome (SARS), which, to enter cells, relies on the proteolytic cleavage of a viral spike protein by the endosomal proteinase cathepsin L. Using alveolar macrophages, we studied uptake of (125)I-amiodarone and (125)I-B2, an analog lacking the lateral group diethylamino-beta-ethoxy, and analyzed the effects of amiodarone on the distribution of endosomal markers and on the uptake of an acidotropic dye. Furthermore, using Vero cells, we tested the impact of amiodarone on the in vitro spreading of the SARS coronavirus. We found that (1) amiodarone associates with different cell membranes and accumulates in acidic organelles; (2) the diethylamino-beta-ethoxy group is an important determinant of uptake; (3) vacuoles forming upon exposure to amiodarone are enlarged late endosomes; (4) amiodarone inhibits the spreading in vitro of SARS coronavirus; and (5) trypsin cleavage of the viral spike protein before infection, which permits virus entry through the plasma membrane, does not impair amiodarone antiviral activity. We conclude that amiodarone alters late compartments of the endocytic pathway and inhibits SARS coronavirus infection by acting after the transit of the virus through endosomes.
DOI: 10.1165/rcmb.2007-0217OC
PubMed: 18314540
Affiliations:
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pubmed:18314540Le document en format XML
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<term>Antiviral Agents (pharmacokinetics)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Cathepsin L</term>
<term>Cathepsins (metabolism)</term>
<term>Cell Membrane (drug effects)</term>
<term>Cell Membrane (metabolism)</term>
<term>Chlorocebus aethiops</term>
<term>Cysteine Endopeptidases (metabolism)</term>
<term>Cytoplasm (drug effects)</term>
<term>Cytoplasm (metabolism)</term>
<term>Endosomes (drug effects)</term>
<term>Endosomes (metabolism)</term>
<term>Humans</term>
<term>Iodine Isotopes (chemistry)</term>
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<term>Macrophages, Alveolar (metabolism)</term>
<term>Macrophages, Alveolar (virology)</term>
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<term>SARS Virus (physiology)</term>
<term>Severe Acute Respiratory Syndrome (drug therapy)</term>
<term>Severe Acute Respiratory Syndrome (metabolism)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Spike Glycoprotein, Coronavirus</term>
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<term>Antiviraux (pharmacologie)</term>
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<term>Cathepsines (métabolisme)</term>
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<term>Cytoplasme (métabolisme)</term>
<term>Endosomes ()</term>
<term>Endosomes (métabolisme)</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
<term>Humains</term>
<term>Isotopes de l'iode ()</term>
<term>Macrophages alvéolaires ()</term>
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<term>Macrophages alvéolaires (virologie)</term>
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<front><div type="abstract" xml:lang="en">Amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation of vacuoles, but uptake and intracellular distribution of the drug, origin of vacuoles, and functional consequences of amiodarone accumulation remain unclear. Our objective was to study amiodarone uptake, clarify the origin of vacuoles, and investigate the effect of amiodarone on the life cycle of the coronavirus responsible for the Severe Acute Respiratory Syndrome (SARS), which, to enter cells, relies on the proteolytic cleavage of a viral spike protein by the endosomal proteinase cathepsin L. Using alveolar macrophages, we studied uptake of (125)I-amiodarone and (125)I-B2, an analog lacking the lateral group diethylamino-beta-ethoxy, and analyzed the effects of amiodarone on the distribution of endosomal markers and on the uptake of an acidotropic dye. Furthermore, using Vero cells, we tested the impact of amiodarone on the in vitro spreading of the SARS coronavirus. We found that (1) amiodarone associates with different cell membranes and accumulates in acidic organelles; (2) the diethylamino-beta-ethoxy group is an important determinant of uptake; (3) vacuoles forming upon exposure to amiodarone are enlarged late endosomes; (4) amiodarone inhibits the spreading in vitro of SARS coronavirus; and (5) trypsin cleavage of the viral spike protein before infection, which permits virus entry through the plasma membrane, does not impair amiodarone antiviral activity. We conclude that amiodarone alters late compartments of the endocytic pathway and inhibits SARS coronavirus infection by acting after the transit of the virus through endosomes.</div>
</front>
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<DateCompleted><Year>2008</Year>
<Month>11</Month>
<Day>03</Day>
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<DateRevised><Year>2020</Year>
<Month>04</Month>
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<Title>American journal of respiratory cell and molecular biology</Title>
<ISOAbbreviation>Am. J. Respir. Cell Mol. Biol.</ISOAbbreviation>
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<ArticleTitle>Amiodarone alters late endosomes and inhibits SARS coronavirus infection at a post-endosomal level.</ArticleTitle>
<Pagination><MedlinePgn>142-9</MedlinePgn>
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<Abstract><AbstractText>Amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation of vacuoles, but uptake and intracellular distribution of the drug, origin of vacuoles, and functional consequences of amiodarone accumulation remain unclear. Our objective was to study amiodarone uptake, clarify the origin of vacuoles, and investigate the effect of amiodarone on the life cycle of the coronavirus responsible for the Severe Acute Respiratory Syndrome (SARS), which, to enter cells, relies on the proteolytic cleavage of a viral spike protein by the endosomal proteinase cathepsin L. Using alveolar macrophages, we studied uptake of (125)I-amiodarone and (125)I-B2, an analog lacking the lateral group diethylamino-beta-ethoxy, and analyzed the effects of amiodarone on the distribution of endosomal markers and on the uptake of an acidotropic dye. Furthermore, using Vero cells, we tested the impact of amiodarone on the in vitro spreading of the SARS coronavirus. We found that (1) amiodarone associates with different cell membranes and accumulates in acidic organelles; (2) the diethylamino-beta-ethoxy group is an important determinant of uptake; (3) vacuoles forming upon exposure to amiodarone are enlarged late endosomes; (4) amiodarone inhibits the spreading in vitro of SARS coronavirus; and (5) trypsin cleavage of the viral spike protein before infection, which permits virus entry through the plasma membrane, does not impair amiodarone antiviral activity. We conclude that amiodarone alters late compartments of the endocytic pathway and inhibits SARS coronavirus infection by acting after the transit of the virus through endosomes.</AbstractText>
</Abstract>
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<ForeName>Konrad</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Novartis Vaccines, Siena, Italy.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Ha</LastName>
<ForeName>Huy Riem</ForeName>
<Initials>HR</Initials>
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<Author ValidYN="Y"><LastName>Ciminale</LastName>
<ForeName>Vincenzo</ForeName>
<Initials>V</Initials>
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<Author ValidYN="Y"><LastName>Spirli</LastName>
<ForeName>Carlo</ForeName>
<Initials>C</Initials>
</Author>
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<ForeName>Giulietta</ForeName>
<Initials>G</Initials>
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<ForeName>Marco</ForeName>
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<ForeName>Andrea</ForeName>
<Initials>A</Initials>
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<Author ValidYN="Y"><LastName>Baritussio</LastName>
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<Initials>A</Initials>
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<Chemical><RegistryNumber>EC 3.4.22.-</RegistryNumber>
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<NameOfSubstance UI="C534281">CTSL protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.22.15</RegistryNumber>
<NameOfSubstance UI="D056668">Cathepsin L</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>N3RQ532IUT</RegistryNumber>
<NameOfSubstance UI="D000638">Amiodarone</NameOfSubstance>
</Chemical>
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<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000638" MajorTopicYN="N">Amiodarone</DescriptorName>
<QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName>
<QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D056668" MajorTopicYN="N">Cathepsin L</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002403" MajorTopicYN="N">Cathepsins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002462" MajorTopicYN="N">Cell Membrane</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName>
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<MeshHeading><DescriptorName UI="D003546" MajorTopicYN="N">Cysteine Endopeptidases</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003593" MajorTopicYN="N">Cytoplasm</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011992" MajorTopicYN="N">Endosomes</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007456" MajorTopicYN="N">Iodine Isotopes</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016676" MajorTopicYN="N">Macrophages, Alveolar</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008562" MajorTopicYN="N">Membrane Glycoproteins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045473" MajorTopicYN="N">SARS Virus</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045169" MajorTopicYN="N">Severe Acute Respiratory Syndrome</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D064370" MajorTopicYN="N">Spike Glycoprotein, Coronavirus</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014617" MajorTopicYN="N">Vacuoles</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014709" MajorTopicYN="N">Vero Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014759" MajorTopicYN="N">Viral Envelope Proteins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2008</Year>
<Month>3</Month>
<Day>4</Day>
<Hour>9</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="medline"><Year>2008</Year>
<Month>11</Month>
<Day>4</Day>
<Hour>9</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="entrez"><Year>2008</Year>
<Month>3</Month>
<Day>4</Day>
<Hour>9</Hour>
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<ArticleIdList><ArticleId IdType="pubmed">18314540</ArticleId>
<ArticleId IdType="pii">2007-0217OC</ArticleId>
<ArticleId IdType="doi">10.1165/rcmb.2007-0217OC</ArticleId>
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<affiliations><list><country><li>Italie</li>
</country>
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<name sortKey="Bruttomesso, Daniela" sort="Bruttomesso, Daniela" uniqKey="Bruttomesso D" first="Daniela" last="Bruttomesso">Daniela Bruttomesso</name>
<name sortKey="Ciminale, Vincenzo" sort="Ciminale, Vincenzo" uniqKey="Ciminale V" first="Vincenzo" last="Ciminale">Vincenzo Ciminale</name>
<name sortKey="Follath, Ferenc" sort="Follath, Ferenc" uniqKey="Follath F" first="Ferenc" last="Follath">Ferenc Follath</name>
<name sortKey="Ha, Huy Riem" sort="Ha, Huy Riem" uniqKey="Ha H" first="Huy Riem" last="Ha">Huy Riem Ha</name>
<name sortKey="Pettenazzo, Andrea" sort="Pettenazzo, Andrea" uniqKey="Pettenazzo A" first="Andrea" last="Pettenazzo">Andrea Pettenazzo</name>
<name sortKey="Saletti, Giulietta" sort="Saletti, Giulietta" uniqKey="Saletti G" first="Giulietta" last="Saletti">Giulietta Saletti</name>
<name sortKey="Schiavon, Marco" sort="Schiavon, Marco" uniqKey="Schiavon M" first="Marco" last="Schiavon">Marco Schiavon</name>
<name sortKey="Spirli, Carlo" sort="Spirli, Carlo" uniqKey="Spirli C" first="Carlo" last="Spirli">Carlo Spirli</name>
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<country name="Italie"><noRegion><name sortKey="Stadler, Konrad" sort="Stadler, Konrad" uniqKey="Stadler K" first="Konrad" last="Stadler">Konrad Stadler</name>
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