Serveur d'exploration sur la COVID en France

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Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia.

Identifieur interne : 001373 ( Main/Exploration ); précédent : 001372; suivant : 001374

Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia.

Auteurs : Andrés Pizzorno [France] ; Blandine Padey [France] ; Thomas Julien [France] ; Sophie Trouillet-Assant [France] ; Aurélien Traversier [France] ; Elisabeth Errazuriz-Cerda [France] ; Julien Fouret [France] ; Julia Dubois [France] ; Alexandre Gaymard [France] ; François-Xavier Lescure [France] ; Victoria Dulière [France] ; Pauline Brun [France] ; Samuel Constant [Suisse] ; Julien Poissy [France] ; Bruno Lina [France] ; Yazdan Yazdanpanah [France] ; Olivier Terrier [France] ; Manuel Rosa-Calatrava [France]

Source :

RBID : pubmed:32835306

Abstract

In the current COVID-19 pandemic context, proposing and validating effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model. Our results emphasize distinctive transcriptional immune signatures between nasal and bronchial HAE, both in terms of kinetics and intensity, hence suggesting putative intrinsic differences in the early response to SARS-CoV-2 infection. Most important, we provide evidence in human-derived tissues on the antiviral efficacy of remdesivir monotherapy and explore the potential of the remdesivir-diltiazem combination as an option worthy of further investigation to respond to the still-unmet COVID-19 medical need.

DOI: 10.1016/j.xcrm.2020.100059
PubMed: 32835306
PubMed Central: PMC7373044


Affiliations:


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Le document en format XML

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<name sortKey="Yazdanpanah, Yazdan" sort="Yazdanpanah, Yazdan" uniqKey="Yazdanpanah Y" first="Yazdan" last="Yazdanpanah">Yazdan Yazdanpanah</name>
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<country xml:lang="fr">France</country>
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<author>
<name sortKey="Padey, Blandine" sort="Padey, Blandine" uniqKey="Padey B" first="Blandine" last="Padey">Blandine Padey</name>
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<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
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</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:affiliation>Signia Therapeutics SAS, Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Signia Therapeutics SAS, Lyon</wicri:regionArea>
<placeName>
<region type="region">Auvergne-Rhône-Alpes</region>
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<author>
<name sortKey="Julien, Thomas" sort="Julien, Thomas" uniqKey="Julien T" first="Thomas" last="Julien">Thomas Julien</name>
<affiliation wicri:level="3">
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
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</placeName>
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<nlm:affiliation>VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
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</placeName>
<orgName type="university">Université Claude Bernard Lyon 1</orgName>
</affiliation>
</author>
<author>
<name sortKey="Trouillet Assant, Sophie" sort="Trouillet Assant, Sophie" uniqKey="Trouillet Assant S" first="Sophie" last="Trouillet-Assant">Sophie Trouillet-Assant</name>
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<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
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</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:affiliation>Laboratoire Commun de Recherche HCL-bioMérieux, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire Commun de Recherche HCL-bioMérieux, Centre Hospitalier Lyon-Sud, Pierre-Bénite</wicri:regionArea>
<wicri:noRegion>Pierre-Bénite</wicri:noRegion>
<wicri:noRegion>Pierre-Bénite</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Traversier, Aurelien" sort="Traversier, Aurelien" uniqKey="Traversier A" first="Aurélien" last="Traversier">Aurélien Traversier</name>
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<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
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<author>
<name sortKey="Errazuriz Cerda, Elisabeth" sort="Errazuriz Cerda, Elisabeth" uniqKey="Errazuriz Cerda E" first="Elisabeth" last="Errazuriz-Cerda">Elisabeth Errazuriz-Cerda</name>
<affiliation wicri:level="4">
<nlm:affiliation>Centre d'Imagerie Quantitative Lyon-Est (CIQLE), Université Claude Bernard Lyon 1, Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre d'Imagerie Quantitative Lyon-Est (CIQLE), Université Claude Bernard Lyon 1, Lyon</wicri:regionArea>
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</placeName>
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</author>
<author>
<name sortKey="Fouret, Julien" sort="Fouret, Julien" uniqKey="Fouret J" first="Julien" last="Fouret">Julien Fouret</name>
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<nlm:affiliation>Signia Therapeutics SAS, Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
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<author>
<name sortKey="Dubois, Julia" sort="Dubois, Julia" uniqKey="Dubois J" first="Julia" last="Dubois">Julia Dubois</name>
<affiliation wicri:level="3">
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Gaymard, Alexandre" sort="Gaymard, Alexandre" uniqKey="Gaymard A" first="Alexandre" last="Gaymard">Alexandre Gaymard</name>
<affiliation wicri:level="3">
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon</wicri:regionArea>
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</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:affiliation>Laboratoire de Virologie, Centre National de Référence des Virus Influenza Sud, Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire de Virologie, Centre National de Référence des Virus Influenza Sud, Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon</wicri:regionArea>
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</affiliation>
</author>
<author>
<name sortKey="Lescure, Francois Xavier" sort="Lescure, Francois Xavier" uniqKey="Lescure F" first="François-Xavier" last="Lescure">François-Xavier Lescure</name>
<affiliation wicri:level="3">
<nlm:affiliation>AP-HP, Infectious and Tropical Diseases Department, Bichat-Claude Bernard University Hospital, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>AP-HP, Infectious and Tropical Diseases Department, Bichat-Claude Bernard University Hospital, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:affiliation>University of Paris, French Institute for Health and Medical Research (INSERM), IAME U1137, Team DesCID, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Paris, French Institute for Health and Medical Research (INSERM), IAME U1137, Team DesCID, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Duliere, Victoria" sort="Duliere, Victoria" uniqKey="Duliere V" first="Victoria" last="Dulière">Victoria Dulière</name>
<affiliation wicri:level="3">
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
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</placeName>
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<nlm:affiliation>VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon</wicri:regionArea>
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<region type="region">Auvergne-Rhône-Alpes</region>
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<settlement type="city">Lyon</settlement>
</placeName>
<orgName type="university">Université Claude Bernard Lyon 1</orgName>
</affiliation>
</author>
<author>
<name sortKey="Brun, Pauline" sort="Brun, Pauline" uniqKey="Brun P" first="Pauline" last="Brun">Pauline Brun</name>
<affiliation wicri:level="3">
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon</wicri:regionArea>
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</placeName>
</affiliation>
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<nlm:affiliation>VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon</wicri:regionArea>
<placeName>
<region type="region">Auvergne-Rhône-Alpes</region>
<region type="old region">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
</placeName>
<orgName type="university">Université Claude Bernard Lyon 1</orgName>
</affiliation>
</author>
<author>
<name sortKey="Constant, Samuel" sort="Constant, Samuel" uniqKey="Constant S" first="Samuel" last="Constant">Samuel Constant</name>
<affiliation wicri:level="1">
<nlm:affiliation>Epithelix Sàrl, Geneva, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Epithelix Sàrl, Geneva</wicri:regionArea>
<wicri:noRegion>Geneva</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Poissy, Julien" sort="Poissy, Julien" uniqKey="Poissy J" first="Julien" last="Poissy">Julien Poissy</name>
<affiliation wicri:level="3">
<nlm:affiliation>Pôle de Réanimation, Hôpital Roger Salengro, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Pôle de Réanimation, Hôpital Roger Salengro, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille</wicri:regionArea>
<placeName>
<region type="region">Hauts-de-France</region>
<region type="old region">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Lina, Bruno" sort="Lina, Bruno" uniqKey="Lina B" first="Bruno" last="Lina">Bruno Lina</name>
<affiliation wicri:level="3">
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon</wicri:regionArea>
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<region type="region" nuts="2">Auvergne-Rhône-Alpes</region>
<region type="old region" nuts="2">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:affiliation>Laboratoire de Virologie, Centre National de Référence des Virus Influenza Sud, Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire de Virologie, Centre National de Référence des Virus Influenza Sud, Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon</wicri:regionArea>
<placeName>
<region type="region">Auvergne-Rhône-Alpes</region>
<region type="old region">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Yazdanpanah, Yazdan" sort="Yazdanpanah, Yazdan" uniqKey="Yazdanpanah Y" first="Yazdan" last="Yazdanpanah">Yazdan Yazdanpanah</name>
<affiliation wicri:level="3">
<nlm:affiliation>AP-HP, Infectious and Tropical Diseases Department, Bichat-Claude Bernard University Hospital, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>AP-HP, Infectious and Tropical Diseases Department, Bichat-Claude Bernard University Hospital, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:affiliation>University of Paris, French Institute for Health and Medical Research (INSERM), IAME U1137, Team DesCID, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Paris, French Institute for Health and Medical Research (INSERM), IAME U1137, Team DesCID, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Terrier, Olivier" sort="Terrier, Olivier" uniqKey="Terrier O" first="Olivier" last="Terrier">Olivier Terrier</name>
<affiliation wicri:level="3">
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon</wicri:regionArea>
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<region type="old region" nuts="2">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Rosa Calatrava, Manuel" sort="Rosa Calatrava, Manuel" uniqKey="Rosa Calatrava M" first="Manuel" last="Rosa-Calatrava">Manuel Rosa-Calatrava</name>
<affiliation wicri:level="3">
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon</wicri:regionArea>
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<region type="region" nuts="2">Auvergne-Rhône-Alpes</region>
<region type="old region" nuts="2">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="4">
<nlm:affiliation>VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon</wicri:regionArea>
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</placeName>
<orgName type="university">Université Claude Bernard Lyon 1</orgName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Cell reports. Medicine</title>
<idno type="eISSN">2666-3791</idno>
<imprint>
<date when="2020" type="published">2020</date>
</imprint>
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<front>
<div type="abstract" xml:lang="en">In the current COVID-19 pandemic
<b>context, proposing and validating</b>
effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model. Our results emphasize distinctive transcriptional immune signatures between nasal and bronchial HAE, both in terms of kinetics and intensity, hence suggesting putative intrinsic differences in the early response to SARS-CoV-2 infection. Most important, we provide evidence in human-derived tissues on the antiviral efficacy of remdesivir monotherapy and explore the potential of the remdesivir-diltiazem combination as an option worthy of further investigation to respond to the still-unmet COVID-19 medical need.</div>
</front>
</TEI>
<pubmed>
<MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM">
<PMID Version="1">32835306</PMID>
<DateRevised>
<Year>2020</Year>
<Month>08</Month>
<Day>24</Day>
</DateRevised>
<Article PubModel="Print">
<Journal>
<ISSN IssnType="Electronic">2666-3791</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>1</Volume>
<Issue>4</Issue>
<PubDate>
<Year>2020</Year>
<Month>Jul</Month>
<Day>21</Day>
</PubDate>
</JournalIssue>
<Title>Cell reports. Medicine</Title>
<ISOAbbreviation>Cell Rep Med</ISOAbbreviation>
</Journal>
<ArticleTitle>Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia.</ArticleTitle>
<Pagination>
<MedlinePgn>100059</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.xcrm.2020.100059</ELocationID>
<Abstract>
<AbstractText>In the current COVID-19 pandemic
<b>context, proposing and validating</b>
effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model. Our results emphasize distinctive transcriptional immune signatures between nasal and bronchial HAE, both in terms of kinetics and intensity, hence suggesting putative intrinsic differences in the early response to SARS-CoV-2 infection. Most important, we provide evidence in human-derived tissues on the antiviral efficacy of remdesivir monotherapy and explore the potential of the remdesivir-diltiazem combination as an option worthy of further investigation to respond to the still-unmet COVID-19 medical need.</AbstractText>
<CopyrightInformation>© 2020 The Author(s).</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Pizzorno</LastName>
<ForeName>Andrés</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Padey</LastName>
<ForeName>Blandine</ForeName>
<Initials>B</Initials>
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<ForeName>Yazdan</ForeName>
<Initials>Y</Initials>
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</AffiliationInfo>
<AffiliationInfo>
<Affiliation>University of Paris, French Institute for Health and Medical Research (INSERM), IAME U1137, Team DesCID, Paris, France.</Affiliation>
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<Initials>O</Initials>
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<Initials>M</Initials>
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<Keyword MajorTopicYN="N">COVID-19</Keyword>
<Keyword MajorTopicYN="N">SARS-CoV-2</Keyword>
<Keyword MajorTopicYN="N">cell ultrastructure remodeling</Keyword>
<Keyword MajorTopicYN="N">coronavirus</Keyword>
<Keyword MajorTopicYN="N">diltiazem</Keyword>
<Keyword MajorTopicYN="N">drug combination</Keyword>
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<CoiStatement>A.P., B.P., T.J., A.T., O.T., and M.R.-C. are co-inventors of a patent application filed by INSERM, CNRS, Université Claude Bernard Lyon 1, and Signia Therapeutics for the repurposing of diltiazem for the treatment of SARS-CoV-2 infections (FR 20/02351). A.P., O.T., and M.R.-C. are co-founders of Signia Therapeutics SAS. S.C. is the founder of Epithelix, the developer and provider of MucilAir HAE. F.-X.L. has received funding for lectures from Gilead Sciences and Merck Sharp & Dohme France, and funding for travel to meetings from Merck Sharp & Dohme France, Astellas, and Eumedica. B.L. is the co-chair of the Global Influenza and RSV Initiative and the chair of the scientific committee of the Global Influenza Hospital Surveillance Network. B.L. received no personal remuneration for these activities. B.L. received travel grants to attend meetings by Abbott, Seegene, Sanofi, and bioMérieux. All of the other authors declare no competing interests.</CoiStatement>
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