Phospholipase A2 as a therapeutic target for treating COVID-19

SARs-CoV2 is a novel coronavirus that created a worldwide pandemic with mortality of over 6.5 million until September 2022. Entry of SARs-CoV2 virus into human cells depends on the binding of spike (S) protein at the protein coat of the virus with the ACE2 receptor of the human cells. After attachment, SARS-CoV2 enters into cells with endocytosis with a membrane fusion that consists of a lipid bilayer with abundant phospholipids. Similarly, after replication in the cells, newly synthesized protein-coat packaged nascent SARS-COV2 virus releases from the cell with exosome formation that also involves membrane fusion. In both cases of entry of the virus into cells and the release of the virus from cells, remodeled phospholipids in the lipid bilayer membranes and phospholipase A2 (PLA2) plays a critical role in such remodeling of lipid architecture. In COVID-19 patients, sPLA2 levels in plasma are exceedingly high with a higher level of arachidonic acid (AA), eicosanoids, and polyunsaturated fatty acids (PUFAs). Increased level of AA and platelet-activating factor (PAF) induces inflammatory responses to induce blood coagulation and “cytokine storm” promoting multiple organ failures. In addition, the increase of PLA2 is positively correlated with disease severity. Thus, targeting PLA2 with PLA2 inhibitors is currently in progress to develop therapies to reduce COVID-19-mediated severity and mortalities.