NAD+ metabolism at the host–virus interface

Nicotinamide adenine dinucleotide (NAD ⁺ ) is one of the most important metabolic coenzymes that not only drives redox reactions and energy production but also acts as a critical substrate for several enzymes involved in immune signalling, DNA repair and epigenetic regulation. Viral infections are known as potent modulators of NAD ⁺ metabolism, with pathogens such as SARS-CoV-2, influenza A virus, Zika virus, herpes simplex virus and human immunodeficiency virus altering NAD ⁺ biosynthesis and consumption to benefit their persistence and replication. In this review, we summarize the current understanding of NAD ⁺ metabolism and its regulatory enzymes: sirtuins, poly (ADP-ribose) polymerases and CD38/CD157. We then discuss the interplay between NAD ⁺ homeostasis and virus infection. Understanding how diverse viruses manipulate NAD ⁺ metabolism could lead to broad-spectrum antiviral strategies grounded in metabolic resilience.