Repurposing of Kinase Inhibitors for Treatment of COVID-19
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Repurposing of Kinase Inhibitors for Treatment of COVID-19 Ellen Weisberg 1,2 & Alexander Parent 1,2 & Priscilla L. Yang 3,4 & Martin Sattler 1,2,5 & Qingsong Liu 6 & Qingwang Liu 6 & Jinhua Wang 7 & Chengcheng Meng 1 & Sara J. Buhrlage 8 & Nathanael Gray 7 & James D. Griffin 1,2
Received: 12 May 2020 / Accepted: 3 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
ABSTRACT 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 lifethreatening. 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 * Ellen Weisberg [email protected]
1
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
2
Department of Medicine, Harvard Medical School, Boston, MA, USA
3
Department of Cancer Cell Biology, Dana-Farber Cancer Institute, Boston, MA, USA
4
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA
5
Department of Surgery, Brigham and Women’s Hospital, Boston, MA, USA
6
High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui, China
7
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA
8
Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
antifibrotic activity. Certain agents are projected to be dualpurpose 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.
KEY WORDS Coronavirus . SARS-CoV-2 . SARS-CoV . MERS-CoV . kinase inhibitors . pharmacokinetics . antiviral therapy . COVID-19
CLINICAL NEED FOR EFFECTIVE TREATMENTS FOR COVID-19 A novel human coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly named 2019-nCoV), emerged in Wuhan, China. The outbreak in the previously unexposed human population was marked by high morbidity caused by SARS-CoV-2 as a result of the associated disease COVID-19 (Corona Virus Disea
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