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

Autor:	Undi RB; Department of Radiation Oncology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA.; Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA., Ahsan N; Department of Chemistry and Biochemistry, University of Oklahoma , Norman, Oklahoma, USA.; Mass Spectrometry, Proteomics and Metabolomics Core Facility, Stephenson Life Sciences Research Center, University of Oklahoma , Norman, Oklahoma, USA., Larabee JL; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA., Darlene-Reuter N; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA., Papin J; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA.; Department of Pathology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA., Dogra S; Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA.; Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA., Hannafon BN; Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA.; Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA., Bronze MS; Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA., Houchen CW; Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA.; Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA.; Department of Internal Medicine, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA.; Department of Veterans Affairs Medical Center , Oklahoma City, Oklahoma, USA., Huycke MM; Department of Radiation Oncology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA.; Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA., Ali N; Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA.; Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA.; Department of Internal Medicine, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA.; Department of Veterans Affairs Medical Center , Oklahoma City, Oklahoma, USA.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2023 Nov 30; Vol. 97 (11), pp. e0119423. Date of Electronic Publication: 2023 Oct 20.
DOI:	10.1128/jvi.01194-23
Abstrakt:	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. Competing Interests: A U.S. patent application (#PCT/US22/77893) is pending entitled, "Composition and Methods for Treating Coronavirus Infections Disease-19 (COVID-19)" with Naushad Ali, Mark M. Huycke, Courtney W. Houchen, and Ram Babu Undi listed as co-inventors. Courtney W. Houchen has an ownership interest with COARE Holdings, Inc. All remaining authors declare no competing interests.
Databáze:	MEDLINE
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