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Liskova, Alena; Samec, Marek; Koklesova, Lenka; Samuel, Samson M.; Zhai, Kevin; Al-Ishaq, Raghad Khalid; Abotaleb, Mariam; Nosal, Vladimir; Kajo, Karol; Ashrafizadeh, Milad; Zarrabi, Ali; Brockmueller, Aranka; Shakibaei, Mehdi; Sabaka, Peter; Mozos, Ioana; Ullrich, David; Prosecky, Robert; La Rocca, Giampiero; Caprnda, Martin; Busselberg, Dietrich; Rodrigo, Luis; Kruzliak, Peter and Kubatka, Peter (2021): Flavonoids against the SARS-CoV-2 induced inflammatory storm. In: Biomedicine & Pharmacotherapy, Vol. 138, 111430

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The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity. The immunomodulatory ability of flavonoids, carried out by the regulation of inflammatory mediators, the inhibition of endothelial activation, NLRP3 inflammasome, toll-like receptors (TLRs) or bromodomain containing protein 4 (BRD4), and the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2), might be beneficial in regulating the cytokine storm during SARS-CoV-2 infection. Moreover, the ability of flavonoids to inhibit dipeptidyl peptidase 4 (DPP4), neutralize 3-chymotrypsin-like protease (3CL(pro)) or to affect gut microbiota to maintain immune response, and the dual action of angiotensin-converting enzyme 2 (ACE-2) may potentially also be applied to the exaggerated inflammatory responses induced by SARS-CoV-2. Based on the previously proven effects of flavonoids in other diseases or on the basis of newly published studies associated with COVID-19 (bioinformatics, molecular docking), it is reasonable to assume positive effects of flavonoids on inflammatory changes associated with COVID-19. This review highlights the current state of knowledge of the utility of

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