A hypothesized role for dysregulated bradykinin signaling in COVID‐19 respiratory complications

Roche, Joseph A.; Roche, Renuka

doi:10.1096/fj.202000967

Cited by 122 publications

(155 citation statements)

References 50 publications

(102 reference statements)

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“…In addition, ACEI is known to potentiate the vasodilator bradykinin (BK). Roche et al (2020) used established and emerging evidence to propose a testable hypothesis that, a vicious positive feedback loop involving dysregulated BK signaling is involved in inflammation, which likely responsible for the severe respiratory complications in COVID-19. Hence, they propose the FDA-approved molecule, icatibant, that might be able to interrupt this feedback loop and, thereby, improve the clinical outcomes (Roche and Roche, 2020).…”

Section: Angiotensin Receptor Blockers (Arbs) and Angiotensin Convertmentioning

confidence: 99%

Update on therapeutic approaches and emerging therapies for SARS-CoV-2 virus

Omolo

Soni

Fasiku

et al. 2020

European Journal of Pharmacology

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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Section: Angiotensin Receptor Blockers (Arbs) and Angiotensin Convertmentioning

confidence: 99%

Update on therapeutic approaches and emerging therapies for SARS-CoV-2 virus

Omolo

Soni

Fasiku

et al. 2020

European Journal of Pharmacology

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“…Of interest, anticoagulant treatment has been reported to be effective in a subset of severe COVID-19 patients [120][121][122], and researchers have determined that the procoagulant transferrin [120][121][122] is upregulated in SARS-CoV-2 infections [83]. Related to such concerns with inflammation and coagulation in COVID-19, there have also recently been proposals centered on ACE2 and the vasopressor system protein bradykinin [53,110]. These are various leads requiring further investigation.…”

Section: Hepcidin Iron Biology and Inflammationmentioning

confidence: 99%

COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein

Ehsani

2020

Biol Direct

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The spike glycoprotein of the SARS-CoV-2 virus, which causes COVID-19, has attracted attention for its vaccine potential and binding capacity to host cell surface receptors. Much of this research focus has centered on the ectodomain of the spike protein. The ectodomain is anchored to a transmembrane region, followed by a cytoplasmic tail. Here we report a distant sequence similarity between the cysteine-rich cytoplasmic tail of the coronavirus spike protein and the hepcidin protein that is found in humans and other vertebrates. Hepcidin is thought to be the key regulator of iron metabolism in humans through its inhibition of the iron-exporting protein ferroportin. An implication of this preliminary observation is to suggest a potential route of investigation in the coronavirus research field making use of an already-established literature on the interplay of local and systemic iron regulation, cytokine-mediated inflammatory processes, respiratory infections and the hepcidin protein. The question of possible homology and an evolutionary connection between the viral spike protein and hepcidin is not assessed in this report, but some scenarios for its study are discussed.

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“…Gastrointestinal symptoms, hypogeusia and anosmia are also frequent. Most commonly, SARS-CoV-2 causes a mild flu-like disease, evolving to critical illness in the form of acute distress respiratory syndrome (ARDS), cytokine storm syndrome and death in predisposed people [ 12 ].…”

Section: Introduction: Sars-cov-2 and Covid-19 Pandemicmentioning

confidence: 99%

Renin Angiotensin System, COVID-19 and Male Fertility: Any Risk for Conceiving?

et al. 2020

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The current knowledge concerning the connection between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the renin–angiotensin system (RAS) system in the male reproductive apparatus is still limited, so dedicated studies are urgently required. Concerns about the male fertility consequences of SARS-CoV-2 infection have started to emerge, since epidemiologic studies observed that this coronavirus affects male patients more frequently and with increased severity, possibly because of the hormone-regulated expression of angiotensin-converting enzyme 2 (ACE2) receptor. A disturbance in fertility is also expected based on studies of the previous SARS-CoV infection, which targets the same ACE2 receptor when entering the host cells. In addition, bioinformatics analyses reveal the abundant expression of ACE2 receptor in the male reproductive tissues, particularly in the testis. It has been proposed that pharmacological intervention favoring the angiotensin-(1–7)/ACE2/Mas receptor pathway and increasing ACE2 expression and activity could greatly prevent inflammatory lesions in this area. Finally, in laboratories performing assisted reproductive technologies it is recommended that more attention should be paid not only to sperm quality but also to safety aspects. Data about the potential infectivity of seminal fluid are in fact conflicting and do not exclude risks for both personnel and patients. The potential infectivity of SARS-CoV-2 in reproductive male tissues should be strongly considered and further investigated for the proper management of in vitro fertilization procedures.

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A hypothesized role for dysregulated bradykinin signaling in COVID‐19 respiratory complications

Cited by 122 publications

References 50 publications

Update on therapeutic approaches and emerging therapies for SARS-CoV-2 virus

Update on therapeutic approaches and emerging therapies for SARS-CoV-2 virus

COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein

Renin Angiotensin System, COVID-19 and Male Fertility: Any Risk for Conceiving?

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