Purinergic signaling: decoding its role in COVID-19 pathogenesis and promising treatment strategies

Abstract

The pathogenesis of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), is complex and involves dysregulated immune responses, inflammation, and coagulopathy. Purinergic signaling, mediated by extracellular nucleotides and nucleosides, has emerged as a significant player in the pathogenesis of COVID-19. Extracellular adenosine triphosphate (ATP), released from damaged or infected cells, is a danger signal triggering immune responses. It activates immune cells, releasing pro-inflammatory cytokines, contributing to the cytokine storm observed in severe COVID-19 cases. ATP also promotes platelet activation and thrombus formation, contributing to the hypercoagulability seen in COVID-19 patients. On the other hand, adenosine, an immunosuppressive nucleoside, can impair anti-viral immune responses and promote tissue damage through its anti-inflammatory effects. Modulating purinergic receptors represents a promising therapeutic strategy for COVID-19. Understanding the role of purinergic signaling in COVID-19 pathogenesis and developing targeted therapeutic approaches can potentially improve patient outcomes. This review focuses on the part of purinergic signaling in COVID-19 pathogenesis and highlights potential therapeutic approaches targeting purinergic receptors.

Keywords: CD39; CD73; COVID-19; Purinergic signaling; Targeted therapy.