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Updated: Jul 12, 2025

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
Blocking of doublecortin-like kinase 1-regulated SARS-CoV-2 replication cycle restores cell signaling network
Ram Babu Undi1,2, Nagib Ahsan3,4, Jason L Larabee5
1Department of Radiation Oncology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA.
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.
Insights
Targeting DCLK1 kinase offers a promising new strategy against severe COVID-19. Inhibiting DCLK1 effectively reduces SARS-CoV-2 replication and inflammation, aiding in treatment development.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Severe COVID-19 and post-acute sequelae are significant health concerns, exacerbated by SARS-CoV-2 variants.
- DCLK1 (Doublecortin-like kinase 1) is upregulated in COVID-19 lungs, promoting viral replication and hyperinflammation.
Purpose of the Study:
- To investigate the role of DCLK1-regulated mechanisms in SARS-CoV-2 replication and pathogenic signaling.
- To evaluate the therapeutic potential of DCLK1 kinase inhibition in COVID-19 treatment.
Main Methods:
- Analysis of DCLK1 expression and its association with viral load and inflammatory markers in COVID-19 patients.
- Pharmacological inhibition of DCLK1 kinase in SARS-CoV-2 infected cells.
- Assessment of viral replication-transcription processes and cellular signaling pathways.
Main Results:
- DCLK1 plays a critical role in driving SARS-CoV-2 replication-transcription and pathogenic signaling.
- Pharmacological inhibition of DCLK1 kinase significantly impedes SARS-CoV-2 replication.
- DCLK1 inhibition effectively counteracts virus-induced alterations in global cell signaling.
Conclusions:
- DCLK1 kinase is a key driver of SARS-CoV-2 pathogenesis.
- Targeting DCLK1 kinase represents a potential therapeutic strategy for managing severe COVID-19 and its sequelae.
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