Therapeutic Potential of P2X7 Purinergic Receptor Modulation in the Main Organs Affected by the COVID-19 Cytokine Storm

Abstract

Defined by the World Health Organization as a global public health pandemic, coronavirus 2019 (COVID-19) has a global impact and has caused the death of thousands of people. The "severe acute respiratory syndrome coronavirus 2" virus (SARS-CoV-2) is the etiologic agent of this disease, which uses the angiotensinconverting enzyme receptor 2 (ACE2) to infect the body, so any organ that expresses the gene ACE2 is a possible target for the new coronavirus. In addition, in severe cases of COVID-19, a cytokine storm occurs, which triggers widespread systemic inflammation due to the uncontrolled release of proinflammatory cytokines. In this perspective, the modulation of purinergic receptors is highlighted in the literature as a possible therapy, considering its application in other viral infections and systemic inflammation. Therefore, this review aims to gather information on the modulation of the P2X7 receptor in the main organs directly affected by the virus and by the cytokine storm: the heart, brain, lung, liver and kidneys. Thus, demonstrating possible therapies for reducing inflammation and the level of morbidity and mortality of COVID-19. In severe cases of COVID-19, SARS-CoV-2 infection is capable of triggering an exacerbated release of cytokines, called a cytokine storm. With this inflammation, or less the direct infection of the virus, the whole organism can be affected. In this way, major and important organs such as the heart, lung, brain, and liver are affected, triggering different pathologies. In this perspective, purinergic signaling is highlighted in the literature for its anti-inflammatory role and has been listed in the pandemic scenario as a potential therapy. Therefore, knowing the expression of the purinergic receptor P2X7 in these tissues, the modulation of its inflammatory activity may be favorable in this severe and systemic condition.

Keywords: COVID-19; P2X7; brain; heart; kidney; liver; therapeutic.