Dissecting lipid metabolism alterations in SARS-CoV-2

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic that has infected over a hundred million people globally. There have been more than two million deaths recorded worldwide, with no end in sight until a widespread vaccination will be achieved. Current research has centred on different aspects of the virus interaction with cell surface receptors, but more needs to be done to further understand its mechanism of action in order to develop a targeted therapy and a method to control the spread of the virus. Lipids play a crucial role throughout the viral life cycle, and viruses are known to exploit lipid signalling and synthesis to affect host cell lipidome. Emerging studies using untargeted metabolomic and lipidomic approaches are providing new insight into the host response to COVID-19 infection. Indeed, metabolomic and lipidomic approaches have identified numerous circulating lipids that directly correlate to the severity of the disease, making lipid metabolism a potential therapeutic target. Circulating lipids play a key function in the pathogenesis of the virus and exert an inflammatory response. A better knowledge of lipid metabolism in the host-pathogen interaction will provide valuable insights into viral pathogenesis and to the development of novel therapeutic targets.

Keywords: COVID-19; Lipid Metabolism; SARS-CoV-2; coronavirus; dyslipidaemia.

Figure 1

Family tree of the seven coronaviruses that infect humans.

Figure 2

Mechanisms of SARS-CoV-2 interaction with host cell and entry. Three different possible endocytic pathways are shown: 1) direct fusion; 2) clathrin-dependent pathway; 3) caveolae- or flotillin-dependent pathway.

Figure 3

Potential mechanisms of SARS-CoV-2 secondary cell infection. Red: exosome-mediated viral cargo release; yellow: lysosome-mediated virus release; green: virus release by alternative secretory pathway.

Figure 4

Steps in viral pathways inhibited by drugs acting on lipid metabolism or exosomes release.

Figure 5

Pathways activated by cytosolic phospholipase A2 (cPLA2) and secretory phospholipase A2 (sPLA2) potentially involved in virus entry and pathogenesis.