TY - JOUR
T1 - Evaluation of molecular mechanisms of riboflavin anti-COVID-19 action reveals anti-inflammatory efficacy rather than antiviral activity
AU - Akasov, Roman A.
AU - Chepikova, Olga E.
AU - Pallaeva, Tatiana N.
AU - Gorokhovets, Neonila V.
AU - Siniavin, Andrei E.
AU - Gushchin, Vladimir A.
AU - Savvateeva, Lyudmila V.
AU - Vinokurov, Ivan A.
AU - Khochenkov, Dmitry A.
AU - Zamyatnin, Andrey A.
AU - Khaydukov, Evgeny V.
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/5
Y1 - 2024/5
N2 - 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.
AB - 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.
KW - Cytokines
KW - Inflammation
KW - PLpro protease
KW - Riboflavin
KW - SARS-CoV-2
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U2 - 10.1016/j.bbagen.2024.130582
DO - 10.1016/j.bbagen.2024.130582
M3 - Article
C2 - 38340879
AN - SCOPUS:85185394453
SN - 0304-4165
VL - 1868
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 5
M1 - 130582
ER -