Purinergic receptor ligands: the cytokine storm attenuators, potential therapeutic agents for the treatment of COVID-19

Abstract

The coronavirus disease-19 (COVID-19), at first, was reported in Wuhan, China, and then rapidly became pandemic throughout the world. Cytokine storm syndrome (CSS) in COVID-19 patients is associated with high levels of cytokines and chemokines that cause multiple organ failure, systemic inflammation, and hemodynamic instabilities. Acute respiratory distress syndrome (ARDS), a common complication of COVID-19, is a consequence of cytokine storm. In this regard, several drugs have been being investigated to suppress this inflammatory condition. Purinergic signaling receptors comprising of P1 adenosine and P2 purinoceptors play a critical role in inflammation. Therefore, activation or inhibition of some subtypes of these kinds of receptors is most likely to be beneficial to attenuate cytokine storm. This article summarizes suggested therapeutic drugs with potential anti-inflammatory effects through purinergic receptors.

Keywords: ARDS; COVID-19; cytokine storm; inflammation; purinergic receptors.

Figure 1.

The role of purinergic signaling on immune system activation. The nucleotide adenosine triphosphate (ATP) and its derivatives released from injured tissues act on various purinoceptor subtypes of P1 and P2. When activated, P2 receptor subtypes (P2X, P2Y) expressed on various immune cells participate in the release of several inflammatory cytokines. P1 receptors (A1, A2, A3) however have an anti-inflammatory effect.