TNKPVI, a Putative Bioaccessible Pharmacophore of Anti-Inflammatory Potato Patatin-Derived Decapeptide DIKTNKPVIF.

Potato protein-derived decapeptide DIKTNKPVIF exerted anti-inflammatory activity in animal models when delivered via intragastric gavage and intraperitoneal injection. However, DIKTNKPVIF is susceptible to hydrolysis in the digestive tract, which will decrease its bioaccessibility and possibly bioactivity. In this study, the anti-inflammatory activity of fragments generated from in silico gastrointestinal enzymatic hydrolysis of DIKTNKPVIF was investigated using the human monocytic (THP-1) cell line. The simulated digestion by pepsin and trypsin released four fragments, DIKTNKPVI, TNKPVIF, DIK and TNKPVI. The peptides lacked the cleavage sites of chymotrypsin. All five peptides were predicted to be non-toxic, which was validated using cytotoxicity assay at 0.25-1 mM peptide concentration. However, the peptides were predicted to possess poor pharmacokinetic profiles, including low passive gastrointestinal absorption and blood-brain barrier permeability. TNKPVIF, DIK and TNKPVI significantly reduced the amount of pro-inflammatory interleukin (IL)-6, IL-8 and tumor necrosis factor in lipopolysaccharide-activated THP-1 cells. Notably, the anti-inflammatory activity of fragment TNKPVI was comparable to that of the parent decapeptide while peptide fragment DIKTNKPVI had no apparent effect on the pro-inflammatory cytokines. This highlights the important role of the C-terminal phenylalanine residue of the parent peptide in the bioactivity. Furthermore, given its activity and the absence of cleavage sites of major digestive proteases, TNKPVI could be the biostable and bioaccessible pharmacophore of potato patatin-derived anti-inflammatory decapeptide DIKTNKPVIF.

Neutrophil Extracellular Traps, Sepsis and COVID-19 - A Tripod Stand.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Majority of COVID-19 patients have mild disease but about 20% of COVID-19 patients progress to severe disease. These patients end up in the intensive care unit (ICU) with clinical manifestations of acute respiratory distress syndrome (ARDS) and sepsis. The formation of neutrophil extracellular traps (NETs) has also been associated with severe COVID-19. Understanding of the immunopathology of COVID-19 is critical for the development of effective therapeutics. In this article, we discuss evidence indicating that severe COVID-19 has clinical presentations consistent with the definitions of viral sepsis. We highlight the role of neutrophils and NETs formation in the pathogenesis of severe COVID-19. Finally, we highlight the potential of therapies inhibiting NETs formation for the treatment of COVID-19.