NAD in COVID-19 and viral infections.

NAD, as an emerging regulator of immune responses during viral infections, may be a promising therapeutic target for coronavirus disease 2019 (COVID-19). In this Opinion, we suggest that interventions that boost NAD levels might promote antiviral defense and suppress uncontrolled inflammation. We discuss the association between low NAD concentrations and risk factors for poor COVID-19 outcomes, including aging and common comorbidities. Mechanistically, we outline how viral infections can further deplete NAD and its roles in antiviral defense and inflammation. We also describe how coronaviruses can subvert NAD-mediated actions via genes that remove NAD modifications and activate the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Finally, we explore ongoing approaches to boost NAD concentrations in the clinic to putatively increase antiviral responses while curtailing hyperinflammation.