Figure 2.

Model for PARP-1 activation in SARS-CoV-2 pathogenesis. Systemic inflammation in SARS-CoV-2 pathogenesis induces immune signaling in cells causing elevated mitochondrial ROS and cytokine response, which triggers PARP-1 transcription and activity. Thereafter, PARP-1 activation PARylates self (autoPARylation) or downstream protein targets by adding Poly (ADP)-ribose residues in a NAD+ dependent manner. Sustained PARylation events under diseased and inflammatory conditions cause declines in intracellular ATP and NAD+ pools, which leads to metabolic dysfunction and cell death, followed by tissue injury, as reported in COVID-19 pathology.