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. 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 and acute lung inflammation . For the first time, the ability of riboflavin at high concentrations (above 50 μM) to inhibit SARS-CoV-2 PLpro protease was demonstrated; however, no inhibition of viral replication in Vero E6 cells was found. At the same time, riboflavin exerted a pronounced anti-inflammatory effect in the polysaccharide-induced inflammation model, both , preventing polysaccharide-induced cell death, and , reducing inflammatory markers (IL-1β, IL-6, and TNF-α) and normalizing lung histology. It is concluded that riboflavin reveals anti-inflammatory rather than antiviral activity for SARS-CoV-2 infection. Riboflavin could be suggested as a promising compound for the therapy of inflammatory diseases of broad origin.

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核黄素抗 COVID-19 作用的分子机制评估揭示了抗炎功效而非抗病毒活性

核黄素（维生素B2）是最重要的水溶性维生素之一，也是参与许多生化过程的辅酶。此前已有研究表明，黄素单核苷酸（一种水溶性核黄素）辅助治疗与 COVID-19 患者临床相关免疫标志物的正常化相关，但这种作用的机制仍不清楚。在这里，研究了核黄素的抗病毒和抗炎作用，以阐明核黄素诱导作用的分子机制。在酶动力学测定中评估了核黄素对重组 SARS-CoV-2 PLpro 的抑制作用，以及对 Vero E6 细胞中 SARS-CoV-2 复制的直接抑制作用，以及在多糖诱导的炎症模型（包括内皮细胞）中的抗炎活性。细胞和急性肺部炎症。首次证明了高浓度（50μM以上）核黄素抑制SARS-CoV-2 PLpro蛋白酶的能力；然而，在 Vero E6 细胞中没有发现病毒复制受到抑制。同时，核黄素在多糖诱导的炎症模型中发挥显着的抗炎作用，既可以防止多糖诱导的细胞死亡，又可以减少炎症标志物（IL-1β、IL-6 和 TNF-α）和使肺组织学正常化。结论是，核黄素对 SARS-CoV-2 感染具有抗炎活性，而非抗病毒活性。核黄素可能被认为是一种有前途的化合物，用于治疗广泛起源的炎症性疾病。