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

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

• nonpeptide bradykinin partial agonist
• drug repurposing
• Covid-19 therapies
• raloxifene