Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Life Sci. 2022 Oct 1;306:120809. doi: 10.1016/j.lfs.2022.120809. Epub 2022 Jul 13.
The highly pathogenic, novel coronavirus disease (COVID-19) outbreak has emerged as a once-in-a-century pandemic with poor consequences, urgently calling for new therapeutics, cures, and supportive interventions. It has already affected over 250 million people worldwide; thereby, there is a need for novel therapies to alleviate the related complications. There is a paradigm shift in developing drugs and clinical practices to combat COVID-19. Several clinical trials have been performed or are testing diverse pharmacological interventions to alleviate viral load and complications such as cytokine release storm (CRS). Kinase-inhibitors have appeared as potential antiviral agents for COVID-19 patients due to their efficacy against CRS. Combination of kinase inhibitors with other therapies can achieve more efficacy against COVID-19. Based on the pre-clinical trials, kinase inhibitors such as Janus kinase-signal transducer and activator of transcription (JAK/STAT) inhibitors, Brutton's tyrosin kinase (BTK) inhibitors, p38 mitogen-activated protein kinases (p38 MAPK) inhibitors, Glycogen synthase kinase 3 (GSK-3) inhibitors can be a promising strategy against COVID-19. Kinase inhibitors possess crucial pharmacological properties for a successful re-purposing in terms of dual anti-inflammatory and anti-viral effects. This review will address the current clinical evidence and the newest discovery regarding the application of kinase inhibitors in COVID-19. An outlook on ongoing clinical trials (clinicaltrials.gov) and unpublished data is also presented here. Besides, Kinase inhibitors' function on COVID-19-mediated CRS is discussed.
高致病性、新型冠状病毒病(COVID-19)疫情的爆发是一场百年一遇的大流行,后果严重,迫切需要新的治疗方法、治愈方法和支持性干预措施。它已经在全球范围内影响了超过 2.5 亿人;因此,需要新的疗法来缓解相关的并发症。在开发药物和临床实践以对抗 COVID-19 方面,出现了一种范式转变。已经进行了或正在测试几种临床试验,以测试多种药理学干预措施来减轻病毒载量和细胞因子释放风暴(CRS)等并发症。由于激酶抑制剂对 CRS 的疗效,它们已成为 COVID-19 患者的潜在抗病毒药物。激酶抑制剂与其他疗法联合使用可以更有效地对抗 COVID-19。基于临床前试验,激酶抑制剂,如 Janus 激酶-信号转导和转录激活因子(JAK/STAT)抑制剂、Brutton 的酪氨酸激酶(BTK)抑制剂、p38 丝裂原激活蛋白激酶(p38 MAPK)抑制剂、糖原合酶激酶 3(GSK-3)抑制剂,可能是对抗 COVID-19 的一种有前途的策略。激酶抑制剂具有双重抗炎和抗病毒作用,在成功重新利用方面具有重要的药理学特性。本综述将讨论关于激酶抑制剂在 COVID-19 中的应用的最新临床证据和最新发现。还介绍了正在进行的临床试验(clinicaltrials.gov)和未发表的数据的展望。此外,还讨论了激酶抑制剂对 COVID-19 介导的 CRS 的作用。