Low dose of emetine as potential anti-SARS-CoV-2 virus therapy: preclinical in vitro inhibition and in vivo pharmacokinetic evidences

被引:0
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作者
Aoli Wang
Yong Sun
Qingwang Liu
Hong Wu
Juan Liu
Jun He
Junling Yu
Qing Qing Chen
Yinglu Ge
Zhuhui Zhang
Chen Hu
Cheng Chen
Ziping Qi
Fengming Zou
Feiyang Liu
Jie Hu
Ming Zhao
Tao Huang
Beilei Wang
Li Wang
Wei Wang
Wenchao Wang
Tao Ren
Jing Liu
Yehuan Sun
Song Fan
Qibing Wu
Chaozhao Liang
Liangdan Sun
Bin Su
Wei Wei
Qingsong Liu
机构
[1] Institute of Health and Medical Technology,Anhui Province Key Laboratory of Medical Physics and Technology, CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology
[2] Hefei Institutes of Physical Science,Hefei Cancer Hospital
[3] Chinese Academy of Sciences,Key Laboratory for Medical and Health of the 13th Five
[4] Chinese Academy of Sciences,Year Plan
[5] Anhui Provincial Center for Disease Control and Prevention,Precision Targeted Therapy Discovery Center
[6] Institute of Technology Innovation,Department of Epidemiology and Health Statistics, School of Public Health
[7] Hefei Institutes of Physical Science,Department of Urology
[8] Chinese Academy of Sciences,Department of Dermatology
[9] Precision Medicine Research Laboratory of Anhui Province,Institute of Physical Science and Information Technology
[10] Anhui Medical University,undefined
[11] The First Affiliated Hospital of Anhui Medical University,undefined
[12] Institute of Urology,undefined
[13] Anhui Medical University,undefined
[14] Anhui Province Key Laboratory of Genitourinary Diseases,undefined
[15] The First Affiliated Hospital of Anhui Medical University,undefined
[16] Key Laboratory of Dermatology (Anhui Medical University),undefined
[17] Ministry of Education,undefined
[18] Key Laboratory of Major Autoimmune Diseases,undefined
[19] Institute of Clinical Pharmacology,undefined
[20] Anhui Medical University,undefined
[21] Key Laboratory of Anti-Inflammatory and Immune Medicine,undefined
[22] Ministry of Education,undefined
[23] Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine,undefined
[24] Anhui University,undefined
来源
Molecular Biomedicine | / 1卷
关键词
Emetine; COVID-19; Anti-SARS-CoV-2 infection therapy; Old drug repurposing;
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摘要
The global pandemic of COVID-19 has attracted extensive drug searching interets for the new coronavirus SARS-CoV-2. Although currently several of clinically used “old” drugs have been repurposed to this new disease for the urgent clinical investigation, there is still great demand for more effective therapies for the anti-infections. Here we report the discovery that an “old” drug Emetine could potently inhibit SARS-CoV-2 virus replication and displayed virus entry blocking effect in Vero cells at low dose. In addition, Emetine could significantly reduce the lipopolysaccharide (LPS) induced interleukin-6 (IL-6) protein level and moderately reduce the tumor necrosis factor (TNF-α) protein level in the M1 polarized THP-1 macrophages. In vivo animal pharmacokinetics (PK) study revealed that Emetine was enriched in the lung tissue and had a long retention time (over 12 h). With 1 mg/kg single oral dose, the effective concentration of Emetine in lung was up to 1.8 μM (mice) and 1.6 μM (rats) at 12 h, which is over 200-fold higher than the EC50 of the drug. The potent in vitro antiviral replication efficacy and the high enrichment in target tissue, combining with the well documented safety profiles in human indicate that low dose of Emetine might be a potentially effective anti-SARS-CoV-2 infection therapy.
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