Molecular Biomedicine (2020-11-01)

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

  • 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

DOI
https://doi.org/10.1186/s43556-020-00018-9
Journal volume & issue
Vol. 1, no. 1
pp. 1 – 9

Abstract

Read online

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.

Keywords