Drug repurposing of anti-infective clinical drugs: Discovery of two potential anti-cytokine storm agents

Biomed Pharmacother. 2020 Nov;131:110643. doi: 10.1016/j.biopha.2020.110643. Epub 2020 Aug 23.

Abstract

Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has been widely spread in the world with a high mortality. Cytokine storm syndrome (CSS) and acute lung injury caused by SARS-CoV-2 infection severely threaten the patients. With the purpose to find effective and low-toxic drugs to mitigate CSS, entecavir and imipenem were identified to reduce TNF-α using a LPS-induced macrophage model from the anti-infective drug library. Entecavir and imipenem efficiently suppressed the release of inflammatory cytokines by partly intervention of NF-κB activity. The acute lung injury was also alleviated and the survival time was prolonged in mice. In addition, entecavir and imipenem inhibited the release of TNF-α and IL-10 in human peripheral blood mononuclear cells (hPBMCs). Collectively, we proposed that entecavir and imipenem might be candidates for the treatment of CSS.

Keywords: Anti-inflammation; COVID-19; Cytokine storm; Drug repurposing; Entecavir; Entercavir: PubChem CID 135398508; Imipenem; Imipenem: PubChem CID 104838.

MeSH terms

  • Acute Lung Injury / drug therapy
  • Acute Lung Injury / virology
  • Animals
  • COVID-19
  • COVID-19 Drug Treatment
  • Coronavirus Infections / complications
  • Coronavirus Infections / drug therapy*
  • Cytokine Release Syndrome / drug therapy*
  • Cytokine Release Syndrome / virology
  • Cytokines / immunology
  • Drug Repositioning
  • Guanine / analogs & derivatives*
  • Guanine / pharmacology
  • Humans
  • Imipenem / pharmacology*
  • Interleukin-10 / immunology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Lipopolysaccharides
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pandemics
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / drug therapy*
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • entecavir
  • Guanine
  • Imipenem