Blocking of doublecortin-like kinase 1-regulated SARS-CoV-2 replication cycle restores cell signaling network
IMPORTANCE: Severe COVID-19 and post-acute sequelae often afflict patients with underlying co-morbidities. There is a pressing need for highly effective treatment, particularly in light of the emergence of SARS-CoV-2 variants. In a previous study, we demonstrated that DCLK1, a protein associated with cancer stem cells, is highly expressed in the lungs of COVID-19 patients and enhances viral production and hyperinflammatory responses. In this study, we report the pivotal role of DCLK1-regulated mechanisms in driving SARS-CoV-2 replication-transcription processes and pathogenic signaling. Notably, pharmacological inhibition of DCLK1 kinase during SARS-CoV-2 effectively impedes these processes and counteracts virus-induced alternations in global cell signaling. These findings hold significant potential for immediate application in treating COVID-19.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:97 |
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| Enthalten in: |
Journal of virology - 97(2023), 11 vom: 30. Nov., Seite e0119423 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Undi, Ram Babu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.12.2023 Date Revised 17.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1128/jvi.01194-23 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Blocking of doublecortin-like kinase 1-regulated SARS-CoV-2 replication cycle restores cell signaling network |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a IMPORTANCE: Severe COVID-19 and post-acute sequelae often afflict patients with underlying co-morbidities. There is a pressing need for highly effective treatment, particularly in light of the emergence of SARS-CoV-2 variants. In a previous study, we demonstrated that DCLK1, a protein associated with cancer stem cells, is highly expressed in the lungs of COVID-19 patients and enhances viral production and hyperinflammatory responses. In this study, we report the pivotal role of DCLK1-regulated mechanisms in driving SARS-CoV-2 replication-transcription processes and pathogenic signaling. Notably, pharmacological inhibition of DCLK1 kinase during SARS-CoV-2 effectively impedes these processes and counteracts virus-induced alternations in global cell signaling. These findings hold significant potential for immediate application in treating COVID-19 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a DCLK1 | |
| 650 | 4 | |a DCLK1-IN-1 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a cell signaling | |
| 650 | 4 | |a host-virus interaction | |
| 650 | 4 | |a interactome | |
| 650 | 4 | |a pathology | |
| 650 | 4 | |a replication-transcription | |
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| 650 | 7 | |a Doublecortin-Like Kinases |2 NLM | |
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| 700 | 1 | |a Ahsan, Nagib |e verfasserin |4 aut | |
| 700 | 1 | |a Larabee, Jason L |e verfasserin |4 aut | |
| 700 | 1 | |a Darlene-Reuter, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Papin, James |e verfasserin |4 aut | |
| 700 | 1 | |a Dogra, Samrita |e verfasserin |4 aut | |
| 700 | 1 | |a Hannafon, Bethany N |e verfasserin |4 aut | |
| 700 | 1 | |a Bronze, Michael S |e verfasserin |4 aut | |
| 700 | 1 | |a Houchen, Courtney W |e verfasserin |4 aut | |
| 700 | 1 | |a Huycke, Mark M |e verfasserin |4 aut | |
| 700 | 1 | |a Ali, Naushad |e verfasserin |4 aut | |
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