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.
J Virol. 2023 Nov 30;97(11):e0119423. doi: 10.1128/jvi.01194-23. Epub 2023 Oct 20.
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.
严重的 COVID-19 和新冠后遗症常使合并基础疾病的患者受苦。鉴于 SARS-CoV-2 变体的出现，我们迫切需要高度有效的治疗方法。在之前的一项研究中，我们证明了与癌症干细胞相关的蛋白 DCLK1 在 COVID-19 患者的肺部中高度表达，并增强了病毒的产生和过度炎症反应。在本研究中，我们报告了 DCLK1 调节机制在驱动 SARS-CoV-2 复制转录过程和致病信号中的关键作用。值得注意的是，在 SARS-CoV-2 期间抑制 DCLK1 激酶的药理学抑制有效地阻止了这些过程，并对抗了病毒诱导的全球细胞信号的改变。这些发现为治疗 COVID-19 提供了直接应用的巨大潜力。
