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Int J Mol Sci ; 22(1)2020 Dec 29.
Article in English | MEDLINE | ID: covidwho-1067749

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.


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