COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3?
Immune response to SARS-CoV-2 and ensuing inflammation pose a huge challenge to the host’s nicotinamide adenine dinucleotide (NAD<sup>+</sup>) metabolism. Humans depend on vitamin B3 for biosynthesis of NAD<sup>+</sup>, indispensable for many metabolic and NAD<sup>+<...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/8/4309 |
| _version_ | 1797445864043577344 |
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| author | Renata Novak Kujundžić |
| author_facet | Renata Novak Kujundžić |
| author_sort | Renata Novak Kujundžić |
| collection | DOAJ |
| description | Immune response to SARS-CoV-2 and ensuing inflammation pose a huge challenge to the host’s nicotinamide adenine dinucleotide (NAD<sup>+</sup>) metabolism. Humans depend on vitamin B3 for biosynthesis of NAD<sup>+</sup>, indispensable for many metabolic and NAD<sup>+</sup>-consuming signaling reactions. The balance between its utilization and resynthesis is vitally important. Many extra-pulmonary symptoms of COVID-19 strikingly resemble those of pellagra, vitamin B3 deficiency (e.g., diarrhoea, 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<sup>+</sup> metabolism in response to the SARS-CoV-2 infection is reviewed, with special emphasis on the differences in the NAD<sup>+</sup> biosynthetic pathway’s efficiency in conditions predisposing for the development of serious COVID-19. SARS-CoV-2 infection-induced NAD<sup>+</sup> depletion and the elevated levels of its metabolites contribute to the development of a systemic disease. Acute liberation of nicotinamide (NAM) in antiviral NAD<sup>+</sup>-consuming reactions potentiates “NAM drain”, cooperatively mediated by nicotinamide N-methyltransferase and aldehyde oxidase. “NAM drain” compromises the NAD<sup>+</sup> salvage pathway’s fail-safe function. The robustness of the host’s NAD<sup>+</sup> 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. |
| first_indexed | 2024-03-09T13:32:55Z |
| format | Article |
| id | doaj.art-324e5e66663940439bd17242e563723a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:32:55Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-324e5e66663940439bd17242e563723a2023-11-30T21:15:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01238430910.3390/ijms23084309COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3?Renata Novak Kujundžić0Laboratory for Epigenomics, Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, CroatiaImmune response to SARS-CoV-2 and ensuing inflammation pose a huge challenge to the host’s nicotinamide adenine dinucleotide (NAD<sup>+</sup>) metabolism. Humans depend on vitamin B3 for biosynthesis of NAD<sup>+</sup>, indispensable for many metabolic and NAD<sup>+</sup>-consuming signaling reactions. The balance between its utilization and resynthesis is vitally important. Many extra-pulmonary symptoms of COVID-19 strikingly resemble those of pellagra, vitamin B3 deficiency (e.g., diarrhoea, 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<sup>+</sup> metabolism in response to the SARS-CoV-2 infection is reviewed, with special emphasis on the differences in the NAD<sup>+</sup> biosynthetic pathway’s efficiency in conditions predisposing for the development of serious COVID-19. SARS-CoV-2 infection-induced NAD<sup>+</sup> depletion and the elevated levels of its metabolites contribute to the development of a systemic disease. Acute liberation of nicotinamide (NAM) in antiviral NAD<sup>+</sup>-consuming reactions potentiates “NAM drain”, cooperatively mediated by nicotinamide N-methyltransferase and aldehyde oxidase. “NAM drain” compromises the NAD<sup>+</sup> salvage pathway’s fail-safe function. The robustness of the host’s NAD<sup>+</sup> 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.https://www.mdpi.com/1422-0067/23/8/4309nicotinamide adenine dinucleotideNAD<sup>+</sup> salvage pathwaynicotinamide N-methyltransferasealdehyde oxidaseobesitydiabetes |
| spellingShingle | Renata Novak Kujundžić COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3? International Journal of Molecular Sciences nicotinamide adenine dinucleotide NAD<sup>+</sup> salvage pathway nicotinamide N-methyltransferase aldehyde oxidase obesity diabetes |
| title | COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3? |
| title_full | COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3? |
| title_fullStr | COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3? |
| title_full_unstemmed | COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3? |
| title_short | COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3? |
| title_sort | covid 19 are we facing secondary pellagra which cannot simply be cured by vitamin b3 |
| topic | nicotinamide adenine dinucleotide NAD<sup>+</sup> salvage pathway nicotinamide N-methyltransferase aldehyde oxidase obesity diabetes |
| url | https://www.mdpi.com/1422-0067/23/8/4309 |
| work_keys_str_mv | AT renatanovakkujundzic covid19arewefacingsecondarypellagrawhichcannotsimplybecuredbyvitaminb3 |