CD38 in the Age of Covid-19: a Medical Perspective.

This medical review addresses the hypothesis that CD38/NADase is at the center of a functional axis (i.e., intracellular Ca2+ mobilization/IFNɣ response/ROS burst) driven by SARS-CoV-2 infection, as already verified in Respiratory Syncytial Virus pathology and CD38 activity in other cellular settings. Key features of the hypothesis are that: i) the substrates of CD38 (e.g., NAD+ and NADP+) are depleted by viral-induced metabolic changes; ii) the products of the enzymatic activity of CD38 (e.g., cADPR/ADPR/NAADP) and related enzymes (e.g., PARPs, Sirtuins, ADP-ribosyl hydrolase) are involved in the anti-viral and proinflammatory response that favors the onset of lung immunopathology (e.g., cytokine storm and organ fibrosis); and iii) the pathological changes induced by this kinetic mechanism may be reduced by distinct modulators of the CD38/NAD+ axis (e.g., CD38 blockers; NAD+ suppliers, among others). This view is supported by arrays of associative basic and applied research data which are herein discussed and integrated with conclusions reported by others in the field of inflammatory, immune, tumor and viral diseases.