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

Springer Science and Business Media LLC - Tập 1 Số 1 - 2020
Aoli Wang1, Yong Sun2, Qingwang Liu3, Hong Wu1, Juan Liu1, Jun He2, Jianing Yu2, Qingqing Chen2, Yinglu Ge2, Zhuhui Zhang2, Changwei Hu1, Chen Cheng1, Qi Zhou1, Fengming Zou1, Feiyang Liu3, Jie Hu3, Ming Zhao4, Tao Huang4, Beilei Wang3, Li Wang3, Wei Wang3, Qianqian Wang3, Tao Ren4, Jing Liu3, Yehuan Sun5, Saijun Fan6, Qibing Wu6, Chaozhao Liang6, Liangdan Sun7,8,9, Bin Su2, Wei Wei10, Qingsong Liu4
1Anhui Province Key Laboratory of Medical Physics and Technology, CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, P. R. China
2Key Laboratory for Medical and Health of the 13th Five-Year Plan, Anhui Provincial Center for Disease Control and Prevention, Hefei, Anhui, 230601, P. R. China
3Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui, 230031, P. R. China
4Precision Targeted Therapy Discovery Center, Institute of Technology Innovation, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230088, P. R. China
5Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
6Department of Urology, The First Affiliated Hospital of Anhui Medical University, Institute of Urology, Anhui Medical University, Anhui Province Key Laboratory of Genitourinary Diseases, Hefei, Anhui, China
7Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
8Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, China
9Key Laboratory of Major Autoimmune Diseases, Hefei, China
10Precision Medicine Research Laboratory of Anhui Province, Hefei, Anhui, 230088, P. R. China

Tóm tắt

AbstractThe 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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