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

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

  • Mol Biomed. 2020;1(1):14. doi: 10.1186/s43556-020-00018-9.
Aoli Wang  # 1 2,  Yong Sun  # 3,  Qingwang Liu  # 2 4 5,  Hong Wu  # 1 2,  Juan Liu  # 1 2,  Jun He 3,  Junling Yu 3,  Qing Qing Chen 3,  Yinglu Ge 3,  Zhuhui Zhang 3,  Chen Hu 1 2,  Cheng Chen 1 2,  Ziping Qi 1 2,  Fengming Zou 1 2,  Feiyang Liu 1 2,  Jie Hu 1 2,  Ming Zhao 4 5,  Tao Huang 4 5,  Beilei Wang 1 2,  Li Wang 1 2,  Wei Wang 1 2 5,  Wenchao Wang 1 2,  Tao Ren 4 5,  Jing Liu 1 2,  Yehuan Sun 6,  Song Fan 7,  Qibing Wu 7,  Chaozhao Liang 7,  Liangdan Sun 8 9 10,  Bin Su 3,  Wei Wei 11,  Qingsong Liu 1 2 4 5 12
Affiliations

Affiliations

  • 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.
  • 2 Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui 230031 P. R. 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.
  • 4 Precision Targeted Therapy Discovery Center, Institute of Technology Innovation, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230088 P. R. China.
  • 5 Precision Medicine Research Laboratory of Anhui Province, Hefei, Anhui 230088 P. R. China.
  • 6 Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China.
  • 7 Department 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.
  • 8 Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 9 Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China.
  • 10 Key Laboratory of Major Autoimmune Diseases, 218 Jixi Road, Hefei, 230022 Anhui 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.
  • 12 Institute of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601 P. R. China.
  • # Contributed equally.
PMID: 34765997 DOI: 10.1186/s43556-020-00018-9
Abstract

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.

Supplementary information: The online version contains supplementary material available at 10.1186/s43556-020-00018-9.

Keywords

Anti-SARS-CoV-2 infection therapy; COVID-19; Emetine; Old drug repurposing.

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