Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Pharm Res. 2020 Aug 10;37(9):167. doi: 10.1007/s11095-020-02851-7.
The outbreak of COVID-19, the pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spurred an intense search for treatments by the scientific community. In the absence of a vaccine, the goal is to target the viral life cycle and alleviate the lung-damaging symptoms of infection, which can be life-threatening. There are numerous protein kinases associated with these processes that can be inhibited by FDA-approved drugs, the repurposing of which presents an alluring option as they have been thoroughly vetted for safety and are more readily available for treatment of patients and testing in clinical trials. Here, we characterize more than 30 approved kinase inhibitors in terms of their antiviral potential, due to their measured potency against key kinases required for viral entry, metabolism, or reproduction. We also highlight inhibitors with potential to reverse pulmonary insufficiency because of their anti-inflammatory activity, cytokine suppression, or antifibrotic activity. Certain agents are projected to be dual-purpose drugs in terms of antiviral activity and alleviation of disease symptoms, however drug combination is also an option for inhibitors with optimal pharmacokinetic properties that allow safe and efficacious co-administration with other drugs, such as antiviral agents, IL-6 blocking agents, or other kinase inhibitors.
新型冠状病毒病(COVID-19)的爆发是由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起的大流行疾病,促使科学界积极寻找治疗方法。在没有疫苗的情况下,目标是针对病毒生命周期并减轻感染导致的肺部损伤症状,这可能危及生命。有许多与这些过程相关的蛋白激酶可以被 FDA 批准的药物抑制,这些药物的再利用是一个诱人的选择,因为它们已经经过了安全性的全面审查,并且更易于为患者治疗和临床试验测试提供。在这里,我们根据已测量的针对病毒进入、代谢或复制所需的关键激酶的抑制能力,对 30 多种已批准的激酶抑制剂的抗病毒潜力进行了描述。我们还强调了具有逆转肺功能不全潜力的抑制剂,因为它们具有抗炎、抑制细胞因子或抗纤维化活性。某些药物有望成为具有抗病毒活性和缓解疾病症状的双重用途药物,但对于具有最佳药代动力学特性的抑制剂,药物联合也是一种选择,这些特性允许与其他药物(如抗病毒药物、IL-6 阻断剂或其他激酶抑制剂)安全有效地联合用药。