Low dose of emetine as potential anti-SARS-CoV-2 virus therapy: preclinical in vitro inhibition and in vivo pharmacokine
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Molecular Biomedicine
RESEARCH
Open Access
Low dose of emetine as potential antiSARS-CoV-2 virus therapy: preclinical in vitro inhibition and in vivo pharmacokinetic evidences Aoli Wang1,2†, Yong Sun3†, Qingwang Liu2,4,5†, Hong Wu1,2†, Juan Liu1,2†, Jun He3, Junling Yu3, Qing Qing Chen3, Yinglu Ge3, Zhuhui Zhang3, Chen Hu1,2, Cheng Chen1,2, Ziping Qi1,2, Fengming Zou1,2, Feiyang Liu1,2, Jie Hu1,2, Ming Zhao4,5, Tao Huang4,5, Beilei Wang1,2, Li Wang1,2, Wei Wang1,2,5, Wenchao Wang1,2, Tao Ren4,5, Jing Liu1,2, Yehuan Sun6, Song Fan7, Qibing Wu7, Chaozhao Liang7, Liangdan Sun8,9,10*, Bin Su3*, Wei Wei11* and Qingsong Liu1,2,4,5,12*
Abstract The global pandemic of COVID-19 has attracted extensive drug searching interets for the new coronavirus SARSCoV-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 (Continued on next page)
* Correspondence: [email protected]; [email protected]; [email protected]; [email protected] † Aoli Wang, Yong Sun, Qingwang Liu, Hong Wu and Juan Liu contributed equally to this work. 8 Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China 3 Key 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 11 Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China 1 Anhui 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 Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as
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