tetano
Editor, Senior Moderator
Pharm Res
. 2020 Aug 10;37(9):167.
doi: 10.1007/s11095-020-02851-7.
Repurposing of Kinase Inhibitors for Treatment of COVID-19
Ellen Weisberg[SUP] 1 2 [/SUP], Alexander Parent[SUP] 3 4 [/SUP], Priscilla L Yang[SUP] 5 6 [/SUP], Martin Sattler[SUP] 3 4 7 [/SUP], Qingsong Liu[SUP] 8 [/SUP], Qingwang Liu[SUP] 8 [/SUP], Jinhua Wang[SUP] 9 [/SUP], Chengcheng Meng[SUP] 3 [/SUP], Sara J Buhrlage[SUP] 10 [/SUP], Nathanael Gray[SUP] 9 [/SUP], James D Griffin[SUP] 3 4 [/SUP]
Affiliations
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 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.
Keywords: COVID-19; Coronavirus; MERS-CoV; SARS-CoV; SARS-CoV-2; antiviral therapy; kinase inhibitors; pharmacokinetics.
. 2020 Aug 10;37(9):167.
doi: 10.1007/s11095-020-02851-7.
Repurposing of Kinase Inhibitors for Treatment of COVID-19
Ellen Weisberg[SUP] 1 2 [/SUP], Alexander Parent[SUP] 3 4 [/SUP], Priscilla L Yang[SUP] 5 6 [/SUP], Martin Sattler[SUP] 3 4 7 [/SUP], Qingsong Liu[SUP] 8 [/SUP], Qingwang Liu[SUP] 8 [/SUP], Jinhua Wang[SUP] 9 [/SUP], Chengcheng Meng[SUP] 3 [/SUP], Sara J Buhrlage[SUP] 10 [/SUP], Nathanael Gray[SUP] 9 [/SUP], James D Griffin[SUP] 3 4 [/SUP]
Affiliations
- PMID: 32778962
- DOI: 10.1007/s11095-020-02851-7
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 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.
Keywords: COVID-19; Coronavirus; MERS-CoV; SARS-CoV; SARS-CoV-2; antiviral therapy; kinase inhibitors; pharmacokinetics.