Abstract
SARS-CoV-2 interacts with ACE2 and infects ACE2-expressing cell leading to the down-regulation of ACE2 and angiotensin II (Ang II) accumulation. The interaction of angiotensin II with its G-protein coupled receptor results in the activation of phosphodiesterase phospholipase C that degrades membrane-bound phosphatidylinositol 4,5-bisphosphate (PIP2) to inositol 1,4, 5-triphosphate (IP3) and diacylglycerol (DAG). This results in the release of cytokines and eicosanoids (leukotrienes, prostaglandin, and thromboxane A2). Inositol triphosphate (IP3)/DAG contribute to Ca2+ release from endoplasmic reticulum (ER) increasing intracellular Ca2+ and activating PKC and NF-kB, PI3K/AKT/mTOR and Ras/MAPK/ERK pathways releasing pro-inflammatory cytokines and regulating the transcription of viral and host proteins. Inflammasome NLRP3 is involved in the pathogenesis of diseases characterized by an excessive maladaptive inflammatory activation such as acute lung injury and recently described in COVID-19. We show how inflammasome function is regulated by DAG, as well as DAG increase results in the lack of B cell-T cell communication and abnormal antibodies function. This article collects for the first time the links betwenn lipids pathways, DAG and the pathophysiology of COVID-19. It described the potential role of mentioned pathways in potential drugs for SARS-CoV-2 infection treatment.