Discovery of a Bradykinin B2 Partial Agonist Profile of Raloxifene in a Drug Repurposing Campaign

Int J Mol Sci. 2020 Dec 29;22(1):257. doi: 10.3390/ijms22010257.

Abstract

Covid-19 urges a deeper understanding of the underlying molecular mechanisms involved in illness progression to provide a prompt therapeutical response with an adequate use of available drugs, including drug repurposing. Recently, it was suggested that a dysregulated bradykinin signaling can trigger the cytokine storm observed in patients with severe Covid-19. In the scope of a drug repurposing campaign undertaken to identify bradykinin antagonists, raloxifene was identified as prospective compound in a virtual screening process. The pharmacodynamics profile of raloxifene towards bradykinin receptors is reported in the present work, showing a weak selective partial agonist profile at the B2 receptor. In view of this new profile, its possible use as a therapeutical agent for the treatment of severe Covid-19 is discussed.

Keywords: Covid-19 therapies; drug repurposing; nonpeptide bradykinin partial agonist; raloxifene.

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / pharmacology*
  • Bradykinin / metabolism
  • CHO Cells
  • COVID-19 Drug Treatment
  • Cricetulus
  • Drug Partial Agonism
  • Drug Repositioning*
  • Inhibitory Concentration 50
  • Ligands
  • Raloxifene Hydrochloride / chemistry
  • Raloxifene Hydrochloride / pharmacokinetics
  • Raloxifene Hydrochloride / pharmacology*
  • Receptor, Bradykinin B2 / agonists*
  • Receptor, Bradykinin B2 / chemistry

Substances

  • Antiviral Agents
  • Ligands
  • Receptor, Bradykinin B2
  • Raloxifene Hydrochloride
  • Bradykinin