COVID-19: NAD+ deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity

Miller, Rachel L.; Wentzel, Annemarie; Richards, Guy A.

doi:10.1016/j.mehy.2020.110044

Cited by 73 publications

(79 citation statements)

References 43 publications

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“…Moreover, neutrophils, macrophages, dendritic cells, B cells, and CD4 + T cells related genes were all up-regulated in infected mice as was also observed in COVID-19 patients ( Figure S2C) (Bost et al, 2020). These results indicated that SARS-CoV-2 infection induces very similar immune processes in both mice and humans (Bost et al, 2020;Chua et al, 2020;Liao et al, 2020;Zhu et al, 2020) Nicotinamide adenine dinucleotide (NAD + ), the cell hydrogen carrier for redox enzymes, plays important roles in multiple metabolic pathways (Miller et al, 2020;Nasi et al, 2020;Omran and Almaliki, 2020). We recently found that PARPs, one of main NAD + -responsive signaling family, were signi cantly up-regulated while NAD + levels were substantially reduced in Zika virus infected mouse brains (Pang et al, manuscript submitted).…”

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confidence: 58%

Treatment of SARS-CoV-2 induced pneumonia with NAD+ in a mouse model

Jiang¹,

Deng²,

Ma³

et al. 2020

Preprint

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The global COVID-19 epidemic has spread rapidly around the world and has already caused the death of more than one million people. As there is yet no vaccine, it is urgent to develop effective strategies to treat COVID-19 patients. Here, we used a mouse-adapted SARS-CoV-2 infection model to explore potential therapeutic targets for SARS-CoV-2 pneumonia. Global gene expression analysis of infected mouse lungs revealed dysregulation of genes associated with NAD+ metabolism, immune response and cell death, similar to that in COVID-19 patients. We therefore investigated the effect of treatment with NAD+ and found that the pneumonia phenotypes, including excessive inflammatory cell infiltration and embolization in SARS-CoV-2 infected lungs were significantly rescued by boosting NAD+ levels. Most notable, cell death was suppressed substantially (>65%) by NAD+ supplementation. Thus, our in vivo mouse study supports trials for treating COVID-19 patients with NAD+ or its precursors.

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supporting

confidence: 58%

Treatment of SARS-CoV-2 induced pneumonia with NAD+ in a mouse model

Jiang¹,

Deng²,

Ma³

et al. 2020

Preprint

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“…Sirtuin activation was reported to reduce influenza A virus titers, while inhibition increased titers [ 100 , 101 ]. Recently, several studies have highlighted the possible role of sirtuin in SARS-CoV-2 induced COVID-19 disease progression [ 102 , 103 ]. Reduced NAD + level and oxidative stress attenuate the protective functions of sirtuin [ 104 ].…”

Section: Astaxanthin As a Potential Adjunctive Supplement In Covid-19mentioning

confidence: 99%

“…Reduced NAD + level and oxidative stress attenuate the protective functions of sirtuin [ 104 ]. NAD + level declines with aging and are further reduced in patients with diabetes, hypertension and obesity thereby reducing the activity of sirtuin [ [102] , [103] , [104] ]. Moreover, SARS-CoV-2 induced oxidative stress results in downregulation of sirtuins to further debilitate its protective functions [ 102 , 103 ].…”

Section: Astaxanthin As a Potential Adjunctive Supplement In Covid-19mentioning

confidence: 99%

“…NAD + level declines with aging and are further reduced in patients with diabetes, hypertension and obesity thereby reducing the activity of sirtuin [ [102] , [103] , [104] ]. Moreover, SARS-CoV-2 induced oxidative stress results in downregulation of sirtuins to further debilitate its protective functions [ 102 , 103 ]. Modulating sirtuin activity levels is thus emerging as a potential therapeutic in experimental models [ 105 ].…”

Section: Astaxanthin As a Potential Adjunctive Supplement In Covid-19mentioning

confidence: 99%

“…Modulating sirtuin activity levels is thus emerging as a potential therapeutic in experimental models [ 105 ]. Drugs that can increase the level of NAD + and thus elevate the functioning of sirtuin in the hyperinflammatory stage may attenuate the CS [ [102] , [103] , [104] , [105] ].…”

Section: Astaxanthin As a Potential Adjunctive Supplement In Covid-19mentioning

confidence: 99%

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Potential of natural astaxanthin in alleviating the risk of cytokine storm in COVID-19

Talukdar

Bhadra

Dattaroy

et al. 2020

Biomedicine & Pharmacotherapy

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Combined Metabolic Activators Accelerates Recovery in Mild‐to‐Moderate COVID‐19

Altay

Arif

et al. 2021

Advanced Science

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COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD + ) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. 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. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. 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.

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COVID-19: NAD+ deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity

Cited by 73 publications

References 43 publications

Treatment of SARS-CoV-2 induced pneumonia with NAD+ in a mouse model

Treatment of SARS-CoV-2 induced pneumonia with NAD+ in a mouse model

Potential of natural astaxanthin in alleviating the risk of cytokine storm in COVID-19

Combined Metabolic Activators Accelerates Recovery in Mild‐to‐Moderate COVID‐19

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