Evaluation of molecular mechanisms of riboflavin anti-COVID-19 action reveals anti-inflammatory efficacy rather than antiviral activity
Copyright © 2024 Elsevier B.V. All rights reserved..
BACKGROUND: Riboflavin (vitamin B2) is one of the most important water-soluble vitamins and a coenzyme involved in many biochemical processes. It has previously been shown that adjuvant therapy with flavin mononucleotide (a water-soluble form of riboflavin) correlates with normalization of clinically relevant immune markers in patients with COVID-19, but the mechanism of this effect remains unclear. Here, the antiviral and anti-inflammatory effects of riboflavin were investigated to elucidate the molecular mechanisms underlying the riboflavin-induced effects.
METHODS: Riboflavin was evaluated for recombinant SARS-CoV-2 PLpro inhibition in an enzyme kinetic assay and for direct inhibition of SARS-CoV-2 replication in Vero E6 cells, as well as for anti-inflammatory activity in polysaccharide-induced inflammation models, including endothelial cells in vitro and acute lung inflammation in vivo.
RESULTS: For the first time, the ability of riboflavin at high concentrations (above 50 μM) to inhibit SARS-CoV-2 PLpro protease in vitro was demonstrated; however, no inhibition of viral replication in Vero E6 cells in vitro was found. At the same time, riboflavin exerted a pronounced anti-inflammatory effect in the polysaccharide-induced inflammation model, both in vitro, preventing polysaccharide-induced cell death, and in vivo, reducing inflammatory markers (IL-1β, IL-6, and TNF-α) and normalizing lung histology.
CONCLUSIONS: It is concluded that riboflavin reveals anti-inflammatory rather than antiviral activity for SARS-CoV-2 infection.
GENERAL SIGNIFICANCE: Riboflavin could be suggested as a promising compound for the therapy of inflammatory diseases of broad origin.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1868 |
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| Enthalten in: |
Biochimica et biophysica acta. General subjects - 1868(2024), 5 vom: 25. März, Seite 130582 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Akasov, Roman A [VerfasserIn] |
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| Links: |
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| Themen: |
059QF0KO0R |
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| Anmerkungen: |
Date Completed 29.03.2024 Date Revised 29.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbagen.2024.130582 |
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NLM368303942 |
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| 245 | 1 | 0 | |a Evaluation of molecular mechanisms of riboflavin anti-COVID-19 action reveals anti-inflammatory efficacy rather than antiviral activity |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Riboflavin (vitamin B2) is one of the most important water-soluble vitamins and a coenzyme involved in many biochemical processes. It has previously been shown that adjuvant therapy with flavin mononucleotide (a water-soluble form of riboflavin) correlates with normalization of clinically relevant immune markers in patients with COVID-19, but the mechanism of this effect remains unclear. Here, the antiviral and anti-inflammatory effects of riboflavin were investigated to elucidate the molecular mechanisms underlying the riboflavin-induced effects | ||
| 520 | |a METHODS: Riboflavin was evaluated for recombinant SARS-CoV-2 PLpro inhibition in an enzyme kinetic assay and for direct inhibition of SARS-CoV-2 replication in Vero E6 cells, as well as for anti-inflammatory activity in polysaccharide-induced inflammation models, including endothelial cells in vitro and acute lung inflammation in vivo | ||
| 520 | |a RESULTS: For the first time, the ability of riboflavin at high concentrations (above 50 μM) to inhibit SARS-CoV-2 PLpro protease in vitro was demonstrated; however, no inhibition of viral replication in Vero E6 cells in vitro was found. At the same time, riboflavin exerted a pronounced anti-inflammatory effect in the polysaccharide-induced inflammation model, both in vitro, preventing polysaccharide-induced cell death, and in vivo, reducing inflammatory markers (IL-1β, IL-6, and TNF-α) and normalizing lung histology | ||
| 520 | |a CONCLUSIONS: It is concluded that riboflavin reveals anti-inflammatory rather than antiviral activity for SARS-CoV-2 infection | ||
| 520 | |a GENERAL SIGNIFICANCE: Riboflavin could be suggested as a promising compound for the therapy of inflammatory diseases of broad origin | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cytokines | |
| 650 | 4 | |a Inflammation | |
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| 650 | 4 | |a Riboflavin | |
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| 700 | 1 | |a Chepikova, Olga E |e verfasserin |4 aut | |
| 700 | 1 | |a Pallaeva, Tatiana N |e verfasserin |4 aut | |
| 700 | 1 | |a Gorokhovets, Neonila V |e verfasserin |4 aut | |
| 700 | 1 | |a Siniavin, Andrei E |e verfasserin |4 aut | |
| 700 | 1 | |a Gushchin, Vladimir A |e verfasserin |4 aut | |
| 700 | 1 | |a Savvateeva, Lyudmila V |e verfasserin |4 aut | |
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| 700 | 1 | |a Zamyatnin, Andrey A |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Khaydukov, Evgeny V |e verfasserin |4 aut | |
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