Niacin in the Covid news

This post reviews a few recent reports in the literature concerning niacin, the other two thirds of CopperOne, and Covid. Most of the latest are nice reviews and novel ideas. Then there is a review that forces us to say, “Wow! CopperOne may modulate our immune response to more infections than Covid-19.

Some very nice reviews,clever in silico, and in lab experiments

Min Su and coauthors (Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin, China) published some interesting ideas concerning the gene overlap of treating colorectal cancer (CRC) and Covid-19 with niacin. [1] We’ve covered a lot of similar concepts in niacin benefits infections. These authors suggested that niacin might actually bind to the inflammatory cytokine IL-1β They came to this conclusion using in silico molecular docking techniques. [1]

The angiotensin converting enzyme 2 is not just for proteolysis of angiotensin II. Camargo and coauthors remind us that this protease can also form heterodimers with the broad neutral ammino acid transporter (B0AT). [2] We are also reminded that mutations in B0AT cause Hartnup Disease which has pellegra like symptoms. If Covid-19 abinds to ACE2 receptors in the small intestine brush borders, the absorption of amino acid precursors of niacin and serotonin might be compromised. [2] Niacin supplementation might be required. [2]

Doroftei and coauthors published an extensive review of niacin/NADH on many biological pathways as they pertain to oxidative stress and Covid-19 infections. [3]

Niacin has been shown to bind to the main 3CLpro protease of Covid-19 and modestly inhibit it’s activity. [4]

And this is how CopperOne works!

Or so we like to think..

This review was authored by Melinda Suchard Dana M. Savulescu of National Institute for Communicable Diseases, Johannesburg, South Africa. Dr Suchard is an expert in the role of indoleamine 2,3-dioxygenase (IDO) in infectious diseases. These authors define “sepsis” as the body’s response to an infection. Septicemia is defined as infectious particles in the blood.

Nicotinamide and macrophage phenotypes

The reducing eqquivalent nicotinamide may be derived from dietary niacin, recycled through existing the reduced version, or synthesized de novo from the amino acid tryptophan. The rate‐limiting enzyme for de novo nicotinamide synthesis is IDO, a haem‐containing intracellular enzyme found predominantly in cells of the macrophage/monocyte lineage. [5]

  • M1 macrophages secrete pro‐inflammatory cytokines such as TNF alpha and interleukin 1‐β.
  • M2 macrophages secrete cytokines such as interleukin‐10, which have immune suppressive functions and play a role in wound healing.

Immunometabolism in macrophages

Resting macrophage utilize the TCA cycle to generate NADH that feeds into the electron transport chain to generate ATP. When stimulated with pathogens macrophage switch to glycolysis. This Warburg metabolism is also found in cancer cells. While not as efficient as aerobic respiration, stopping at pyruvate allows the macrophage to conserve pyruvate for synthesis of other biological materials.

Right images of the role of copper in the mitochondria. Left from ref [5]
A closer look at pathways intersecting with NAD+

The authors looked at pathways regulated by NAD+, the oxidized form of NADH + H+,. from the standpoint of IDO kicking in, or not, when dietary niacin is insufficient. These pathways include:

  • PARP ADP ribose polymerase enzymes use NAD+ as a substrate to repair DNA double strand breaks.
  • NAD+ also plays a key role in autophagy through partnering with sirtuins, which are NAD‐dependent deacetylases.
  • CD38 can act as an extracellular receptor for NAD+ and an enzyme that produces ADP ribose from NAD+.
  • NAD+ is released from cells during early inflammation where it may interact with CD38 on T and B lymphocytes. [5] CD38 may also be found on airway smooth muscle cells. [5]
  • M1 macrophage activation occurred simultaneously with NAD+ depletion .
  • Nuclear NAD+ may affect transcription of key inflammatory genes.

Looking forward

The Suchardand Savulescu review on NAD+ pathways in macrophage may change how we view a lot of things beyond Covid and the immune system.

The added component of CD38 signalling, that we are only now becoming aware of, adds a whole new component of how Cu+ and nicotinic acid may act in synergy as an immune modulator agent. And a lot more!

References

  1. Li, R., Li, Y., Liang, X., Yang, L., Su, M., & Lai, K. P. (2021). Network Pharmacology and bioinformatics analyses identify intersection genes of niacin and COVID-19 as potential therapeutic targets. Briefings in bioinformatics, 22(2), 1279–1290. PMC free article
  2. Camargo SMR, Vuille-Dit-Bille RN, Meier CF, Verrey F. (2020) ACE2 and gut amino acid transport. Clin Sci (Lond). 2020 Nov 13;134(21):2823-2833.
  3. Doroftei, B., Ilie, O. D., Cojocariu, R. O., Ciobica, A., Maftei, R., Grab, D., Anton, E., McKenna, J., Dhunna, N., & Simionescu, G. (2020). Minireview Exploring the Biological Cycle of Vitamin B3 and Its Influence on Oxidative Stress: Further Molecular and Clinical Aspects. Molecules (Basel, Switzerland), 25(15), 3323. PMC free article
  4. Gao, J., Zhang, L., Liu, X., Li, F., Ma, R., Zhu, Z., Zhang, J., Wu, J., Shi, Y., Pan, Y., Ge, Y., & Ruan, K. (2020). Repurposing Low-Molecular-Weight Drugs against the Main Protease of Severe Acute Respiratory Syndrome Coronavirus 2. The journal of physical chemistry letters, 11(17), 7267–7272. Free PMC article
  5. Suchard MS, Savulescu DM. Nicotinamide pathways as the root cause of sepsis – an evolutionary perspective on macrophage energetic shifts. FEBS J. 2021 Mar 8. Free article

Published by BL

I like to write educational websites

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