Bradykinin-target therapies in SARS-CoV-2 infection: current evidence and perspectives.

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.

• Authors: Manuele Figueiredo da Silva, João Xavier de Araújo-Júnior, Edeildo Ferreira da Silva-Júnior, Luana Heimfarth, Paulo Ricardo Martins-Filho, Jullyana de Souza Siqueira Quintans, Lucindo José Quintans-Júnior
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 395 Issue 3 Pg. 275-283 (03 2022) ISSN: 1432-1912 [Electronic] Germany
• PMID: 35089406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Interleukin-6
• Bradykinin

Topics

• Bradykinin (antagonists & inhibitors, physiology)
• COVID-19 (etiology)
• Drug Repositioning
• Humans
• Interleukin-6 (antagonists & inhibitors)
• SARS-CoV-2 (drug effects)
• COVID-19 Drug Treatment