PMC:7796052 / 1774-3453 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7796052","sourcedb":"PMC","sourceid":"7796052","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7796052","text":"Treatment of Covid-19 urges a deeper understanding of the underlying molecular mechanisms involved in disease progression to provide a prompt therapeutical response with an adequate use of available drugs, including drug repurposing. Indeed, there is a number of ongoing clinical trials to test the efficacy of diverse FDA-approved drugs against Covid-19. Among them, a few involve assessment of the therapeutic efficacy of IL-6 inhibition, unfortunately without reporting conclusive results [9,10,11]. Recently, it was proposed that dysregulated bradykinin (BK) signaling could be the trigger of the cytokine storm observed in patients with severe Covid-19 [12,13,14,15]. The rational for this hypothesis relies on the increased availability of BK and its metabolite des-Arg9-BK in Covid-19 patients, due to the downregulation of angiotensin converting enzyme 2 (ACE2), the entry protein of SARS-Cov-2 [16]. Indeed, ACE2 downregulation increases the amount of angiotensin I processed by the angiotensin-converting enzyme (ACE) with a concomitant decrease of its degradation activity on BK. Moreover, levels of des-Arg9-BK are also increased due to the diminished degradative activity of ACE2 caused by its downregulation [12]. The BK hypothesis is consistent with the observed elevated levels of IL-6 in Covid-19 patients [17]. This new perspective suggests that inhibition of BK signaling may be a suitable therapy to avoid the cytokine storm and its consequences. Indeed, as a proof of principle, preliminary results from a limited study suggests that inhibition of the BK signaling is associated with a decrease of the oxygen supplementation needed by Covid-19 patients 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