Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia
© 2020 The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1 |
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| Enthalten in: |
Cell reports. Medicine - 1(2020), 4 vom: 21. Juli, Seite 100059 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pizzorno, Andrés [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.02.2022 Date Revised 07.12.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.xcrm.2020.100059 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31408746X |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Julien, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Trouillet-Assant, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Traversier, Aurélien |e verfasserin |4 aut | |
| 700 | 1 | |a Errazuriz-Cerda, Elisabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Fouret, Julien |e verfasserin |4 aut | |
| 700 | 1 | |a Dubois, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Gaymard, Alexandre |e verfasserin |4 aut | |
| 700 | 1 | |a Lescure, François-Xavier |e verfasserin |4 aut | |
| 700 | 1 | |a Dulière, Victoria |e verfasserin |4 aut | |
| 700 | 1 | |a Brun, Pauline |e verfasserin |4 aut | |
| 700 | 1 | |a Constant, Samuel |e verfasserin |4 aut | |
| 700 | 1 | |a Poissy, Julien |e verfasserin |4 aut | |
| 700 | 1 | |a Lina, Bruno |e verfasserin |4 aut | |
| 700 | 1 | |a Yazdanpanah, Yazdan |e verfasserin |4 aut | |
| 700 | 1 | |a Terrier, Olivier |e verfasserin |4 aut | |
| 700 | 1 | |a Rosa-Calatrava, Manuel |e verfasserin |4 aut | |
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