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布鲁顿酪氨酸激酶作为 COVID-19 治疗靶点的相关性。

Relevance of the Bruton Tyrosine Kinase as a Target for COVID-19 Therapy.

机构信息

Department of Surgery, McGill University, Montreal, Quebec, Canada.

Department of Pharmacy, Sulaimani Technical Institute, Al Sulaymaniyah, Kurdistan Region, Iraq.

出版信息

Mol Cancer Res. 2021 Apr;19(4):549-554. doi: 10.1158/1541-7786.MCR-20-0814. Epub 2020 Dec 16.

Abstract

The outbreak of the novel coronavirus disease 2019 (COVID-19) has emerged as one of the biggest global health threats worldwide. As of October 2020, more than 44 million confirmed cases and more than 1,160,000 deaths have been reported globally, and the toll is likely to be much higher before the pandemic is over. There are currently little therapeutic options available and new potential targets are intensively investigated. Recently, Bruton tyrosine kinase (BTK) has emerged as an interesting candidate. Elevated levels of BTK activity have been reported in blood monocytes from patients with severe COVID-19, compared with those from healthy volunteers. Importantly, various studies confirmed empirically that administration of BTK inhibitors (acalabrutinib and ibrutinib) decreased the duration of mechanical ventilation and mortality rate for hospitalized patients with severe COVID-19. Herein, we review the current information regarding the role of BTK in severe acute respiratory syndrome coronavirus 2 infections and the suitability of its inhibitors as drugs to treat COVID-19. The use of BTK inhibitors in the management of COVID-19 shows promise in reducing the severity of the immune response to the infection and thus mortality. However, BTK inhibition may be contributing in other ways to inhibit the effects of the virus and this will need to be carefully studied.

摘要

新型冠状病毒病 2019(COVID-19)的爆发已成为全球最大的全球健康威胁之一。截至 2020 年 10 月,全球已报告超过 4400 万例确诊病例和超过 116 万例死亡,在大流行结束之前,死亡人数可能会更高。目前可用的治疗方法很少,新的潜在目标正在深入研究。最近,布鲁顿酪氨酸激酶(BTK)已成为一个有趣的候选者。与健康志愿者相比,严重 COVID-19 患者的血液单核细胞中报告的 BTK 活性升高。重要的是,各种研究经验证证实,BTK 抑制剂(阿卡鲁替尼和依鲁替尼)的给药可降低住院严重 COVID-19 患者的机械通气时间和死亡率。在此,我们回顾了关于 BTK 在严重急性呼吸综合征冠状病毒 2 感染中的作用及其抑制剂作为治疗 COVID-19 的药物的适用性的最新信息。BTK 抑制剂在 COVID-19 管理中的使用有望降低对感染的免疫反应的严重程度,从而降低死亡率。但是,BTK 抑制可能以其他方式抑制病毒的作用,这需要仔细研究。

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