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.
【저자키워드】 COVID-19, Drug repurposing, ACE2, bradykinin, Des-Arg9-BK, Kallikrein system., 【초록키워드】 Treatment, coronavirus disease, Drug repurposing, SARS-CoV-2, pathology, Coronavirus disease 2019, Cytokine storm, coronavirus, Cytokines, IL-6, SARS-COV-2 infection, peptide, drugs, Intervention, adjuvants, cytokine, drug, severe acute respiratory syndrome Coronavirus, pathophysiology, bradykinin, management, Human monoclonal antibody, pathway, Icatibant, respiratory tract, receptor, utility, disease, mechanism, COVID-19 patients, Signaling, noscapine, Clinical efficacy, Interaction, reduction, acute respiratory syndrome, Activation, Kallikrein, ecallantide, treatment of COVID-19, modulation, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, complex, COVID-19-related complications, clinical conditions, clinical condition, respiratory disorders, blockers, fatal disease, prominence, pharmacological, infect, respiratory disorder, lanadelumab, IMPROVE, caused, modulate, explain, modulating, the cytokine storm, 【제목키워드】 SARS-CoV-2, therapy, Evidence, Perspective,