tetano
Editor, Senior Moderator
Naunyn Schmiedebergs Arch Pharmacol
. 2022 Jan 28.
doi: 10.1007/s00210-022-02206-6. Online ahead of print.
Bradykinin-target therapies in SARS-CoV-2 infection: current evidence and perspectives
Manuele Figueiredo da Silva[SUP] 1 [/SUP], João Xavier de Araújo-Júnior[SUP] 1 [/SUP], Edeildo Ferreira da Silva-Júnior[SUP] 2 [/SUP], Luana Heimfarth[SUP] 3 [/SUP], Paulo Ricardo Martins-Filho[SUP] 4 [/SUP], Jullyana de Souza Siqueira Quintans[SUP] 5 [/SUP], Lucindo José Quintans-Júnior[SUP] 5 [/SUP]
Affiliations
Abstract
Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that preferentially infects the respiratory tract. Bradykinin (BK) is a hypotensive substance that recently emerged as one of the mechanisms to explain COVID-19-related complications. Concerning this, in this review, we try to address the complex link between BK and pathophysiology of COVID-19, investigating the role of this peptide as a potential target for pharmacological modulation in the management of SARS-CoV-2. The pathology of COVID-19 may be more a result of the BK storm than the cytokine storm, and which BK imbalance is a relevant factor in the respiratory disorders caused by SARS-CoV-2 infection. Regarding this, an interesting point of intervention for this disease is to modulate BK signaling. Some drugs, such as icatibant, ecallantide, and noscapine, and even a human monoclonal antibody, lanadelumab, have been studied for their potential utility in COVID-19 by modulating BK signaling. The interaction of the BK pathway and the involvement of cytokines such as IL-6 and IL1 may be key to the use of blockers, even if only as adjuvants. In fact, reduction of BK, mainly DABK, is considered a relevant strategy to improve clinical conditions of COVID-19 patients. In this context, despite the current unproven clinical efficacy, drugs repurposing that block B1 or B2 receptor activation have gained prominence for the treatment of COVID-19 in the world.
Keywords: ACE2; Bradykinin; COVID-19; Des-Arg9-BK; Drug repurposing; Kallikrein system.
. 2022 Jan 28.
doi: 10.1007/s00210-022-02206-6. Online ahead of print.
Bradykinin-target therapies in SARS-CoV-2 infection: current evidence and perspectives
Manuele Figueiredo da Silva[SUP] 1 [/SUP], João Xavier de Araújo-Júnior[SUP] 1 [/SUP], Edeildo Ferreira da Silva-Júnior[SUP] 2 [/SUP], Luana Heimfarth[SUP] 3 [/SUP], Paulo Ricardo Martins-Filho[SUP] 4 [/SUP], Jullyana de Souza Siqueira Quintans[SUP] 5 [/SUP], Lucindo José Quintans-Júnior[SUP] 5 [/SUP]
Affiliations
- PMID: 35089406
- DOI: 10.1007/s00210-022-02206-6
Abstract
Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that preferentially infects the respiratory tract. Bradykinin (BK) is a hypotensive substance that recently emerged as one of the mechanisms to explain COVID-19-related complications. Concerning this, in this review, we try to address the complex link between BK and pathophysiology of COVID-19, investigating the role of this peptide as a potential target for pharmacological modulation in the management of SARS-CoV-2. The pathology of COVID-19 may be more a result of the BK storm than the cytokine storm, and which BK imbalance is a relevant factor in the respiratory disorders caused by SARS-CoV-2 infection. Regarding this, an interesting point of intervention for this disease is to modulate BK signaling. Some drugs, such as icatibant, ecallantide, and noscapine, and even a human monoclonal antibody, lanadelumab, have been studied for their potential utility in COVID-19 by modulating BK signaling. The interaction of the BK pathway and the involvement of cytokines such as IL-6 and IL1 may be key to the use of blockers, even if only as adjuvants. In fact, reduction of BK, mainly DABK, is considered a relevant strategy to improve clinical conditions of COVID-19 patients. In this context, despite the current unproven clinical efficacy, drugs repurposing that block B1 or B2 receptor activation have gained prominence for the treatment of COVID-19 in the world.
Keywords: ACE2; Bradykinin; COVID-19; Des-Arg9-BK; Drug repurposing; Kallikrein system.