What do secreted phospholipases A2 have to offer in combat against different viruses up to SARS-CoV-2?

Abstract

Secreted phospholipases A 2 (sPLA 2 s) form a widespread group of structurally-related enzymes that catalyse the hydrolysis of the sn -2 ester bond of glycerophospholipids to produce free fatty acids and lysophospholipids. In humans, nine catalytically active and two inactive sPLA 2 proteins have been identified. These enzymes play diverse biological roles, including host defence against bacteria, parasites and viruses. Several of these endogenous sPLA 2 s may play a defensive role in viral infections, as they display in vitro antiviral activity by both direct and indirect mechanisms. However, endogenous sPLA 2 s may also exert an offensive and negative role, dampening the antiviral response or promoting inflammation in animal models of viral infection. Similarly, several exogenous sPLA 2 s, most of them from snake venoms and other animal venoms, possess in vitro antiviral activities. Thus, both endogenous and exogenous sPLA 2 s may be exploited for the development of new antiviral substances or as therapeutic targets for antagonistic drugs that may promote a more robust antiviral response. In this review, the antiviral versus proviral role of both endogenous and exogenous sPLA 2 s against various viruses including coronaviruses is presented. Based on the highlighted developments in this area of research, possible directions of future investigation are envisaged. One of them is also a possibility of exploiting sPLA 2 s as biological markers of the severity of the Covid-19 pandemic caused by SARS-CoV-2 infection.

The free fatty acid–binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron

“…During early stages of coronavirus infection, PLA2s are activated as evidenced by increased cellular levels of lysophospholipids and FFAs such as LA, arachidonic acid, oleic acid, and palmitoleic acid in both SARS-CoV-2-infected cell cultures and SARS-CoV-2-infected patients (16,(24)(25)(26). A central regulator of lipidome remodeling during β-CoV infection is cPLA2.…”

Hyperinflammation, apoptosis, and organ damage

“…sPLA2 levels are correlated to clinical severity in the COVID-19 population, including a pediatric subset. 17,19,110–114 Even though they represent only a fraction of the total severe COVID-19 cases, pediatric COVID-19 has become a major public health issue. Diorio et al 115 demonstrated an elevation in cytokine profiles associated with multisystem inflammatory syndrome in children (MIS-C), in children infected with COVID-19, suggesting that early identification of inflammatory factors like sPLA2 is valuable to monitor disease severity.…”

The Free Fatty Acid-Binding Pocket is a Conserved Hallmark in Pathogenic β-Coronavirus Spike Proteins from SARS-CoV to Omicron

“…During early stages of coronavirus infection, phospholipase A2s (PLA2s) are activated as evidenced by increased cellular levels of lysophospholipids and FFAs such as LA, arachidonic acid, oleic acid and palmitoleic acid in both SARS-CoV-2 infected cell cultures and SARS-CoV-2 infected patients (16, [24][25][26]. A central regulator of lipidome remodeling during -CoV infection is cytoplasmic PLA2 (cPLA2).…”