Life Sci . Recent clinical findings on the role of kinase inhibitors in COVID-19 management

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Life Sci


. 2022 Jul 13;120809.
doi: 10.1016/j.lfs.2022.120809. Online ahead of print.
Recent clinical findings on the role of kinase inhibitors in COVID-19 management


Zahra Malekinejad ¹ , Amir Baghbanzadeh ² , Ailar Nakhlband ³ , Behzad Baradaran ² , Sevda Jafai ⁴ , Yasin Bagheri ⁵ , Faezeh Raei ⁶ , Soheila Montazersaheb ⁷ , Raheleh Farahzadi ⁸



Affiliations

• PMID: 35841979
• PMCID: PMC9278000
• DOI: 10.1016/j.lfs.2022.120809

Abstract

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 An outlook on ongoing clinical trials (clinicaltrials.gov) and unpublished data is also presented here.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.

Keywords: BTK; COVID-19; CRS; GSK-3; JAK/STAT; Kinase inhibitor; Signaling; p38 MAPK.