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

Jiang, Yisheng; Deng, Yong-Qiang; Ma, Tiantian; Pang, Huanhuan; Hu, Zhiyuan; Qin, Cheng‐Feng; Xu, Zhiheng

doi:10.21203/rs.3.rs-96999/v1

Cited by 3 publications

(3 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(32-34) NAD+ deficiency is present in most of the comorbid conditions associated with severe disease and mortality, and COVID-19 itself further decreases NAD+ by increasing its utilisation as an energy source through inflammation and through the activation of the DNA repair enzyme poly [ADP-ribose] polymerase 1 (PARP1). (35,36) This deficiency may persist following the acute illness and be enhanced by low grade on-going inflammation, particularly in those with the comorbidities described earlier. (37) Where NAD+ is depleted and exogenous sources are not available, tryptophan is utilised via the kynurenine pathway to enhance production which, in addition to its role in SIRT activation, is an essential cofactor for cell survival and even more so in metabolically active tissues (Figure 1).…”

Section: Pathogenesis Of Pacsmentioning

confidence: 98%

“…The resultant depletion of tryptophan is exacerbated by the genetic upregulation of the kynurenine pathway in COVID infection and by the increase in proinflammatory cytokines such as TNFα and γ-interferon. (36,38) This decreases the availability of serotonin and melatonin, which are important for control of mood, temperature regulation, sleep cycle, sensory stimulation, nociception and nerve regulation. (40)(41)(42) Metabolites of tryptophan catabolism so produced are implicated in many disease processes and may explain various symptoms of PACS, including autonomic dysfunction.…”

Section: Nad+ Biosynthetic Pathwaysmentioning

confidence: 99%

See 1 more Smart Citation

Post-Acute COVID-19 Sequelae – ‘COVID Long Hauler’

Richards¹,

Wentzel²,

Miller³

et al. 2021

WJCM

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus-2 infection manifests with an acute illness of varying severity and unpredictable mortality. Those who survive may develop a more prolonged disease process called post-acute COVID-19 sequelae which causes considerable disability regardless of the severity of the acute disease. Two phenotypes have been described. First, those with persistent organ dysfunction related to the degree of the inflammatory response and second those with less well defined, but no less troublesome symptoms, that considerably impact the quality of life. This review discusses both phenotypes and the proposed mechanisms and also explores possible therapies for this condition.

show abstract

Section: Pathogenesis Of Pacsmentioning

confidence: 98%

Section: Nad+ Biosynthetic Pathwaysmentioning

confidence: 99%

Post-Acute COVID-19 Sequelae – ‘COVID Long Hauler’

Richards¹,

Wentzel²,

Miller³

et al. 2021

WJCM

View full text Add to dashboard Cite

show abstract

“…In animals, nicotinamide mononucleotide preserves mitochondrial function and promotes survival from haemorrhagic shock [89]. Importantly, in a mouse model of SARS‐CoV‐2 infection, nicotinamide administration reduced inflammatory cell aggregates, emboli and cell death [90] We will focus further on the experience with administration of vitamin B3 and related compounds to humans.…”

Section: Novel Therapies For Sepsismentioning

confidence: 99%

Nicotinamide pathways as the root cause of sepsis – an evolutionary perspective on macrophage energetic shifts

Suchard

Savulescu

2021

The FEBS Journal

View full text Add to dashboard Cite

Divergent pathways of macrophage metabolism occur during infection, notably switching between oxidative phosphorylation and aerobic glycolysis (Warburg-like metabolism). Concurrently, macrophages shift between alternate and classical activation. A key enzyme upregulated in alternatively activated macrophages is indoleamine 2,3-dioxygenase, which converts tryptophan to kynurenine for de novo synthesis of nicotinamide. Nicotinamide can be used to replenish cellular NAD + supplies. We hypothesize that an insufficient cellular NAD + supply is the root cause of metabolic shifts in macrophages. We assert that manipulation of nicotinamide pathways may correct deleterious immune responses. We propose evaluation of nicotinamide (Vitamin B3) and analogues, including isoniazid, nicotinamide mononucleotide and nicotinamide riboside, as potential therapy for infectious causes of sepsis, including COVID-19.

show abstract

Comorbidity-associated glutamine deficiency is a predisposition to severe COVID-19

Matsuyama

Yoshinaga²,

Shibue

et al. 2021

Cell Death Differ

View full text Add to dashboard Cite

SARS-CoV-2 vaccinations have greatly reduced COVID-19 cases, but we must continue to develop our understanding of the nature of the disease and its effects on human immunity. Previously, we suggested that a dysregulated STAT3 pathway following SARS-Co-2 infection ultimately leads to PAI-1 activation and cascades of pathologies. The major COVID-19-associated metabolic risks (old age, hypertension, cardiovascular diseases, diabetes, and obesity) share high PAI-1 levels and could predispose certain groups to severe COVID-19 complications. In this review article, we describe the common metabolic profile that is shared between all of these high-risk groups and COVID-19. This profile not only involves high levels of PAI-1 and STAT3 as previously described, but also includes low levels of glutamine and NAD + , coupled with overproduction of hyaluronan (HA). SARS-CoV-2 infection exacerbates this metabolic imbalance and predisposes these patients to the severe pathophysiologies of COVID-19, including the involvement of NETs (neutrophil extracellular traps) and HA overproduction in the lung. While hyperinflammation due to proinflammatory cytokine overproduction has been frequently documented, it is recently recognized that the immune response is markedly suppressed in some cases by the expansion and activity of MDSCs (myeloid-derived suppressor cells) and FoxP3 + Tregs (regulatory T cells). The metabolomics profiles of severe COVID-19 patients and patients with advanced cancer are similar, and in high-risk patients, SARS-CoV-2 infection leads to aberrant STAT3 activation, which promotes a cancer-like metabolism. We propose that glutamine deficiency and overproduced HA is the central metabolic characteristic of COVID-19 and its high-risk groups. We suggest the usage of glutamine supplementation and the repurposing of cancer drugs to prevent the development of severe COVID-19 pneumonia.

show abstract

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

Cited by 3 publications

References 21 publications

Post-Acute COVID-19 Sequelae – ‘COVID Long Hauler’

Post-Acute COVID-19 Sequelae – ‘COVID Long Hauler’

Nicotinamide pathways as the root cause of sepsis – an evolutionary perspective on macrophage energetic shifts

Comorbidity-associated glutamine deficiency is a predisposition to severe COVID-19

Contact Info

Product

Resources

About