Figure 1.

SARS-CoV-2 infection and subsequent inflammation alters neutrophil chromatin, ultimately producing neutrophil extracellular traps that are vulnerable to attenuation through PAD-4 inhibition. Neutrophil chromatin is non-pathologically found in a condensed state mediated through arginine (R) residues. In an inflammatory state, condensed chromatin is modified to a decondensed form through histone citrullination (Cit) by peptidylarginine deiminases (PAD-4), thereby neutralizing DNA-backbone interactions. Decondensed chromatin and various proteins not displayed in the image, produce “net-like” occlusions that mount in the vessel lumen, resulting in thrombus formation. Use of various PAD-4 inhibitors cease the formation of decondensed chromatin at varying affinities, a necessary chromatin modification for NETs formation.