Release of potential pro-inflammatory peptides from SARS-CoV-2 spike glycoproteins in neutrophil-extracellular traps

Abstract

COVID-2019 has progressed in around 10-15% of patients to an acute respiratory distress syndrome characterized by extensive pulmonary inflammation and elevated production of pro-inflammatory cytokines. Neutrophil activation seems to be crucial in the initiation and perpetuation of this exacerbated lung inflammation. However, the precise mechanisms by which this activation occurs remain yet elusive. To this end, this in silico study tried to identify potential proinflammatory inducing peptides (PIPs) produced by the action of the elastase released in neutrophil-extracellular traps over SARS-CoV-2 particles. We found nine potential PIPs exclusive from the SARS-CoV-2, showing homology against T cell recognition epitopes. Moreover, 78 percent of these exclusive PIPs were found produced by the enzymatic cleavage on the spike glycoproteins, suggesting that high PIP concentrations might be released following SARS-CoV-2 huge replication rate. Therefore, these PIPs might play a role in the exacerbated inflammatory response observed in some patients. Highlights• Nine potential PIPs were predicted exclusive from the SARS-CoV-2.• SARS-CoV-2 PIPs showed homology against T cell recognition epitopes. • Most of PIPs were produced by enzymatic cleavage of the spike glycoproteins. • The release of these PIPs might be related to the increased inflammatory response observed in the patients.

The role of 5-lipoxygenase in the pathophysiology of COVID-19 and its therapeutic implications

“…A higher number of blood neutrophils (also called neutrophilia) contributes to the initiation and progression of pulmonary inflammation in later stages. In relation to SARS-COV-2, Blanco-Miguez et al, have identified 9 potential proinflammatory inducing peptides (PIPS) that may be linked to an increase in host inflammation [26].…”

“…In response to SARS-CoV-2, neutrophils release inflammatory peptides, suggesting their association with the pulmonary strike [26]. Neutrophils accumulate early at the site of inflammation followed by a sustained population of monocytes, macrophages, and lymphocytes.…”