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The innate immune system relies on NAD to fight infection, including viral infection, so it is no surprise that some viruses, including COVID, dramatically depress NAD levels when they strike, and that sustaining NAD levels can support the immune system's ability to fight back.

ARTICLE: Can NAD Protect Me From COVID?


Here are the studies:

Sep 2, 2023

Immunity - Viral Infection - COVID

Nitric Oxide

NAD(+)-boosting compounds enhance nitric oxide production and prevent oxidative stress in endothelial cells exposed to plasma from patients with COVID-19

Freeberg, Kaitlin A.


NAD + precursors prevent COVID-19 plasma-induced endothelial cell dysfunction and hold promise as therapies for COVID-19-related vascular dysfunction...Co-incubation with NR abolished COVID-19-induced reductions in NO production and oxidative stress (both p > 0.05 vs. control). Co-treatment with NMN produced similar results. Our findings suggest the circulating milieu of patients with COVID-19 promotes endothelial cell dysfunction, characterized by lower NO bioavailability, greater ROS bioactivity, and NAD(+) depletion. Supplementation with NAD(+) precursors may exert a protective effect against COVID-19-evoked endothelial cell dysfunction and oxidative stress.

Aug 7, 2023

Immunity - Viral Infection

Bioscience Reports

The kynurenine pathway of tryptophan metabolism: a neglected therapeutic target of COVID-19 pathophysiology and immunotherapy

Badawy, Abdulla Abu-Bakr


While most COVID-19 therapeutic efforts have understandably focused on vaccines from the public health perspective, less emphasis was directed at other therapeutic options either independently or conjointly with vaccination. Current evidence strongly suggests that theKynurenine pathway of tryptophan metabolism is the top target of COVID-19 infection and a major determinant of its pathophysiology... Depletion of NAD+ and ATP are the end result of COVID-19 infection...Replenishing NAD+ levels (in COVID) can be achieved by using suitable NAD+ precursors. Careful choice of precursors is however important. Use of Trp is inadvisable for two reasons: increased production of Kyn metabolites and the powerful AhR agonist IPA. Similarly, nicotinic acid is unlikely to contribute to NAD+ replenishment, given that the Preiss-Handler pathway will also be blocked. This leaves nicotinamide or its riboside...

Oct 22, 2022

Viral Infection - COVID

Nature Metabolism

Innate metabolic responses against viral infections

Palmer, Clovis S.


Metabolic disorders may increase the vulnerability of individuals to SARS-CoV-2 and worsen disease prognosis...Low levels of circulating NAD+ are reported in severe COVID-19...Coronavirus infection can deplete cellular NAD+ levels, and boosting NAD+ with NAD precursors has been shown to enhance the antiviral activities of PARP isozymes...NAD+ is also essential for critical host antioxidant and anti-inflammatory responses. Thus, therapeutic reinforcement of the NAD+ system has been proposed as a potential prophylaxis approach against viruses such as SARS-CoV-2 infection...Ultimately, the outcome of this ‘tug-of-war’ [between the virus and the immune system both drawing down NAD] is likely to be influenced by the nutritional status of the host....

Apr 13, 2022

Viral Infection ⎼ COVID

International Journal of Molecular Science

COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3?

Kujundzik, Renata


...Many extra-pulmonary symptoms of COVID-19 strikingly resemble those of pellagra, vitamin B3 deficiency (e.g., diarrhea, dermatitis, oral cavity and tongue manifestations, loss of smell and taste, mental confusion). In most developed countries, pellagra is successfully eradicated by vitamin B3 fortification programs. Thus, conceivably, it has not been suspected as a cause of COVID-19 symptoms. Here, the deregulation of the NAD+ metabolism in response to the SARS-CoV-2 infection is reviewed, with special emphasis on the differences in the NAD+ biosynthetic pathway’s efficiency in conditions predisposing for the development of serious COVID-19... The robustness of the host’s NAD+ salvage pathway, prior to the SARS-CoV-2 infection, is an important determinant of COVID-19 severity and persistence of certain symptoms upon resolution of infection.

Feb 11, 2022

Viral Infection ⎼ COVID

Trends in Immunology

NAD+ in COVID-19 and viral infections

Zheng, Minyan


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.

Jan 5, 2022

Viral Infection - COVID

Journal of Molecular Structure

Molecular docking and dynamics studies of Nicotinamide Riboside as a potential multi-target nutraceutical against SARS-CoV-2 entry, replication, and transcription: A new insight

Esam, Zohreh


...Nicotinamide riboside (NR), which is a naturally occurring analogue of Niacin (vitamin B3), is expected to have therapeutic effects on COVID-19 due to its super close structural similarity to the proven RdRp inhibitors...In the current study, the resulted scores from molecular docking and dynamics simulations as the primary determinative factor as well as the observed reliable binding modes have demonstrated that Nicotinamide Riboside and its active metabolite NMN can target human ACE2 and IMPDH, along with the viral Spro, Mpro, PLpro, and on top of all, RdRp as a potential competitive inhibitor.

Jan 3, 2022

Viral Infection⎼ COVID

Nature Metabolism

Viral infection as an NAD+ battlefield

Brenner, Charles


Coronavirus replication results in expenditure of nicotinamide adenine dinucleotide (NAD+), the central catalyst of cellular metabolism, in the innate response to infection. Repletion of NAD+ levels has the potential to enhance antiviral responses.

Sep 30, 2021

Viral Infection ⎼ COVID

Saudi Journal of Biological Sciences

Potential role of nicotinamide analogues against SARS-COV-2 target proteins

Arora, Mandeep Kumar


COVID-19 is caused by ‘severe acute respiratory syndrome coronavirus 2′ (SARS-CoV-2)...The present study screens nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) as potential inhibitors of this present generation coronavirus infection using an in-silico approach...We expect a possible therapeutic efficacy of NR in the treatment of COVID-19.

Sep 8, 2021

Viral Infection ⎼ COVID

Advanced Science

Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19 (Phase 3 study)

Altay, Ozlem


...Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery from COVID-19 on ambulatory patients using a cocktail that included nicotinamide riboside as an NAD precursor. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group...The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.

Aug 12, 2021

Viral Infection ⎼ Zika

Nature Metabolism

Aberrant NAD+ metabolism underlies Zika virus–induced microcephaly

Pang, Huan Huan


Zika virus (ZIKV) infection during pregnancy can cause microcephaly in newborns, yet the underlying mechanisms remain largely unexplored. Here, we reveal extensive and large-scale metabolic reprogramming events in ZIKV-infected mouse brains by performing a multi-omics study comprising transcriptomics, proteomics, phosphoproteomics and metabolomics approaches. Our proteomics and metabolomics analyses uncover dramatic alteration of nicotinamide adenine dinucleotide (NAD+)-related metabolic pathways, including oxidative phosphorylation, TCA cycle and tryptophan metabolism. Phosphoproteomics analysis indicates that MAPK and cyclic GMP–protein kinase G signaling may be associated with ZIKV-induced microcephaly. Notably, we demonstrate the utility of our rich multi-omics datasets with follow-up in vivo experiments, which confirm that boosting NAD+ by NAD+ or nicotinamide riboside supplementation alleviates cell death and increases cortex thickness in ZIKV-infected mouse brains. Nicotinamide riboside supplementation increases the brain and body weight as well as improves the survival in ZIKV-infected mice. Our study provides a comprehensive resource of biological data to support future investigations of ZIKV-induced microcephaly and demonstrates that metabolic alterations can be potentially exploited for developing therapeutic strategies.

May 19, 2021

Viral Infection - Metabolism

Frontiers in Molecular Biosciences

NAD+ Metabolism, Metabolic Stress, and Infection

Groth, Benjamin


NAD+ levels also appear to decline with age, which may render the elderly more susceptible to various infections as well as age-associated disorders..Interestingly, several pathogens also appear to target the NAD+ metabolic network upon infection.

Jan 13, 2021

Viral Infection ⎼ COVID

Journal of Biological Chemistry

Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity

Heer, Colin


...Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with [coronavirus model] induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of a [coronavirus model] that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.

Nov 6, 2020

Immunity - Viral Infection - Nicotinamide - Metabolism

FEBS Journal

Mechanisms to Reduce the Cytotoxicity of Pharmacological Nicotinamide Concentrations in the Pathogenic Fungus Candida Albicans

Ghugari, Rahul


Although the results presented in this manuscript challenge the notion that NAM may prove valuable to treat fungal infections, there remain a number of potentially valuable strategies to augment the therapeutic efficacy of NAM.

Jul 11, 2012

Viral Infection - Herpes

Journal of Virology

Herpes Simplex Virus 1 Infection Activates Poly(ADP-Ribose) Polymerase and Triggers the Degradation of Poly(ADP-Ribose) Glycohydrolase

Grady, Sarah L


We have found that Herpes simplex virus 1 infection activates PARP-1/2 and that this results in the massive depletion of NAD+.

NAD Research - Viral Infection

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