COVID-19 and purinergic signaling: the need for investigation
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COVID-19 and purinergic signaling: the need for investigation Andréia Machado Cardoso 1 Received: 16 June 2020 / Accepted: 6 July 2020 # Springer Nature B.V. 2020
Keywords Purinergic signaling . COVID-19 . Coronavirus
This letter aims to raise the need for investigation about the role of purinergic signaling in Coronavirus disease 19 (Covid19) pathophysiology. Moreover, experimental model tests with P2X blockers, P1 agonists, and/or enzyme inhibitors could be useful to unveil the possible mechanisms underlying COVID-19 physiopathology related to the role of purinergic system components. From now, what we know is that acute respiratory issues are the primary cause of mortality of Coronavirus disease 19 (Covid-19) patients. No effective treatment is available for instance, and even the disease pathophysiology is poorly understood. Respiratory distress is caused and sustained by a massive release of proinflammatory cytokines that triggers an uncontrolled inflammation accompanied by lung edema and disseminated coagulation [5]. The regulation of the immune system cells and platelets functions plays a central role in COVID-19 disease [5]. Nowadays it is known that purinergic signaling can modulate platelet activation, cellular trafficking of immune cells as well as the release of pro- and antiinflammatory cytokines [2, 4]. Recently, it has been proposed that P2X7 antagonist administration could be an option for critically ill Covid-19 patients due its special role in the release of cytokines by macrophages [1]. It has also been suggested that therapeutic benefit of purinergic modulators, such as dipyridamole (A2A receptor agonist), must be investigated because it targets multiple pathways that have been implicated in COVID-19 pathogenesis [3]. Indeed, Kanthi research group is developing protocols to launch multiple clinical trials with dipyridamole at different stages of COVID-19 (NCT04391179, available on http:// clinicaltrials.gov) [3]. These two recent published papers * Andréia Machado Cardoso [email protected]; [email protected] 1
Federal University of Fronteira Sul, Medicine Course, Graduate Program in Biomedical Sciences, Member of the Brazilian Purine Club, Campus Chapecó, Chapecó, SC, Brazil
highlight the importance of investigating purinergic system in COVID-19 physiopathology. It is important to note that blood extracellular purines and adenosine, components of the purinergic system, are increasingly recognized as key mediators of activation and/or inhibition of circulating immune cells and platelets adhesion. Since ATP and adenosine, as well as other nucleotides, play a role in immune system and platelet activation and have opposite effects, proper regulation of purinergic signaling by ectonucleotidases and adenosine deaminase (ADA) may be crucial to modulate immune cells and platelet functions [2, 4]. Once released by a damaged tissue into the blood, ATP can be broken down by a cascade of ectonucleotidases into ADP, AMP, and adenosine. By regulating the concentrations of e
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