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2020 ; 143
(ä): 109886
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What would Sérgio Ferreira say to your physician in this war against COVID-19:
How about kallikrein/kinin system?
#MMPMID32504925
Nicolau LAD
; Magalhães PJC
; Vale ML
Med Hypotheses
2020[Oct]; 143
(ä): 109886
PMID32504925
show ga
Coronavirus disease 2019 (COVID-19) is an infectious disease with fast spreading
all over the world caused by the SARS-CoV-2 virus which can culminate in a severe
acute respiratory syndrome by the injury caused in the lungs. However, other
organs can be also damaged. SARS-CoV-2 enter into the host cells using the
angiotensin-converting enzyme 2 (ACE2) as receptor, like its ancestor SARS-CoV.
ACE2 is then downregulated in lung tissues with augmented serum levels of ACE2 in
SARS-CoV-2 patients. Interestingly, ACE2(+) organs reveal the symptomatic
repercussions, which are signals of the infection such as dry cough, shortness of
breath, heart failure, liver and kidney damage, anosmia or hyposmia, and
diarrhea. ACE2 exerts a chief role in the renin-angiotensin system (RAS) by
converting angiotensin II to angiotensin-(1-7) that activates Mas receptor,
inhibits ACE1, and modulates bradykinin (BK) receptor sensitivity, especially the
BK type 2 receptor (BKB2R). ACE2 also hydrolizes des-Arg(9)-bradykinin (DABK), an
active BK metabolite, agonist at BK type 1 receptors (BKB1R), which is
upregulated by inflammation. In this opinion article, we conjecture a dialogue by
the figure of Sérgio Ferreira which brought together basic science of classical
pharmacology and clinical repercussions in COVID-19, then we propose that in the
course of SARS-CoV-2 infection: i) downregulation of ACE2 impairs the angiotensin
II and DABK inactivation; ii) BK and its metabolite DABK seems to be in elevated
levels in tissues by interferences in kallikrein/kinin system; iii) BK1 receptor
contributes to the outbreak and maintenance of the inflammatory response; iv)
kallikrein/kinin system crosstalks to RAS and coagulation system, linking
inflammation to thrombosis and organ injury. We hypothesize that targeting the
kallikrein/kinin system and BKB1R pathway may be beneficial in SARS-CoV-2
infection, especially on early stages. This route of inference should be
experimentally verified by SARS-CoV-2 infected mice.