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Blocking of doublecortin-like kinase 1-regulated SARS-CoV-2 replication cycle restores cell signaling network.


ABSTRACT:

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.

SUBMITTER: Undi RB 

PROVIDER: S-EPMC10688311 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Blocking of doublecortin-like kinase 1-regulated SARS-CoV-2 replication cycle restores cell signaling network.

Undi Ram Babu RB   Ahsan Nagib N   Larabee Jason L JL   Darlene-Reuter Nicole N   Papin James J   Dogra Samrita S   Hannafon Bethany N BN   Bronze Michael S MS   Houchen Courtney W CW   Huycke Mark M MM   Ali Naushad N  

Journal of virology 20231020 11


<h4>Importance</h4>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-regu  ...[more]

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