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.