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Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia

Andrés Pizzorno, Blandine Padey, Thomas Julien, Sophie Trouillet-Assant, Aurélien Traversier, Elisabeth Errazuriz-Cerda, Julien Fouret, View ORCID ProfileJulia Dubois, Alexandre Gaymard, François-Xavier Lescure, Victoria Dulière, Pauline Brun, Samuel Constant, Julien Poissy, Bruno Lina, Yazdan Yazdanpanah, View ORCID ProfileOlivier Terrier, Manuel Rosa-Calatrava
doi: https://doi.org/10.1101/2020.03.31.017889
Andrés Pizzorno
1Virologie et Pathologie Humaine - VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
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Blandine Padey
1Virologie et Pathologie Humaine - VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
2Signia Therapeutics SAS, Lyon, France
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Thomas Julien
1Virologie et Pathologie Humaine - VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
3VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
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Sophie Trouillet-Assant
1Virologie et Pathologie Humaine - VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
4Laboratoire Commun de Recherche HCL-bioMérieux, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
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Aurélien Traversier
1Virologie et Pathologie Humaine - VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
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Elisabeth Errazuriz-Cerda
5Centre d’Imagerie Quantitative Lyon-Est (CIQLE), Université Claude Bernard Lyon 1, Lyon, France
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Julien Fouret
2Signia Therapeutics SAS, Lyon, France
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Julia Dubois
1Virologie et Pathologie Humaine - VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
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  • ORCID record for Julia Dubois
Alexandre Gaymard
1Virologie et Pathologie Humaine - VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
6Laboratoire de Virologie, Centre National de Référence des virus Influenza Sud, Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France
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François-Xavier Lescure
7AP-HP, Infectious and Tropical Diseases Department, Bichat-Claude Bernard University Hospital, Paris, France
8University of Paris, French Institute for Health and Medical Research (INSERM), IAME, U1137, Team DesCID, Paris, France
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Victoria Dulière
1Virologie et Pathologie Humaine - VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
2Signia Therapeutics SAS, Lyon, France
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Pauline Brun
1Virologie et Pathologie Humaine - VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
2Signia Therapeutics SAS, Lyon, France
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Samuel Constant
9Epithelix Sàrl, Geneva, Switzerland
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Julien Poissy
10Pôle de Réanimation, Hôpital Roger Salengro, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille, France
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Bruno Lina
1Virologie et Pathologie Humaine - VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
6Laboratoire de Virologie, Centre National de Référence des virus Influenza Sud, Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France
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Yazdan Yazdanpanah
7AP-HP, Infectious and Tropical Diseases Department, Bichat-Claude Bernard University Hospital, Paris, France
8University of Paris, French Institute for Health and Medical Research (INSERM), IAME, U1137, Team DesCID, Paris, France
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Olivier Terrier
1Virologie et Pathologie Humaine - VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
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  • ORCID record for Olivier Terrier
  • For correspondence: olivier.terrier@univ-lyon1.fr manuel.rosa-calatrava@univ-lyon1.fr
Manuel Rosa-Calatrava
1Virologie et Pathologie Humaine - VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France
2Signia Therapeutics SAS, Lyon, France
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  • For correspondence: olivier.terrier@univ-lyon1.fr manuel.rosa-calatrava@univ-lyon1.fr
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Abstract

In the current COVID-19 pandemic context, proposing and validating effective treatments represents a major challenge. However, the lack of biologically relevant pre-clinical experimental models of SARS-CoV-2 infection as a complement of classic cell lines represents a major barrier for scientific and medical progress. Here, we advantageously used human reconstituted airway epithelial models of nasal or bronchial origin to characterize viral infection kinetics, tissue-level remodeling of the cellular ultrastructure and transcriptional immune signatures induced by SARS-CoV-2. Our results underline the relevance of this model for the preclinical evaluation of antiviral candidates. Foremost, we provide evidence on the antiviral efficacy of remdesivir and the therapeutic potential of the remdesivir-diltiazem combination as a rapidly available option to respond to the current unmet medical need imposed by COVID-19.

One Sentence Summary New insights on SARS-CoV-2 biology and drug combination therapies against COVID-19.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 02, 2020.
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Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia
Andrés Pizzorno, Blandine Padey, Thomas Julien, Sophie Trouillet-Assant, Aurélien Traversier, Elisabeth Errazuriz-Cerda, Julien Fouret, Julia Dubois, Alexandre Gaymard, François-Xavier Lescure, Victoria Dulière, Pauline Brun, Samuel Constant, Julien Poissy, Bruno Lina, Yazdan Yazdanpanah, Olivier Terrier, Manuel Rosa-Calatrava
bioRxiv 2020.03.31.017889; doi: https://doi.org/10.1101/2020.03.31.017889
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Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia
Andrés Pizzorno, Blandine Padey, Thomas Julien, Sophie Trouillet-Assant, Aurélien Traversier, Elisabeth Errazuriz-Cerda, Julien Fouret, Julia Dubois, Alexandre Gaymard, François-Xavier Lescure, Victoria Dulière, Pauline Brun, Samuel Constant, Julien Poissy, Bruno Lina, Yazdan Yazdanpanah, Olivier Terrier, Manuel Rosa-Calatrava
bioRxiv 2020.03.31.017889; doi: https://doi.org/10.1101/2020.03.31.017889

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