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

Secreted phospholipases A₂ (sPLA₂s) 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 sPLA₂ proteins have been identified. These enzymes play diverse biological roles, including host defence against bacteria, parasites and viruses. Several of these endogenous sPLA₂s may play a defensive role in viral infections, as they display in vitro antiviral activity by both direct and indirect mechanisms. However, endogenous sPLA₂s may also exert an offensive and negative role, dampening the antiviral response or promoting inflammation in animal models of viral infection. Similarly, several exogenous sPLA₂s, most of them from snake venoms and other animal venoms, possess in vitro antiviral activities. Thus, both endogenous and exogenous sPLA₂s 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 sPLA₂s 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 sPLA₂s as biological markers of the severity of the Covid-19 pandemic caused by SARS-CoV-2 infection.