Flavonoids against the SARS-CoV-2 induced inflammatory storm

Liskova, Alena and Samec, Marek and Koklesova, Lenka and Samuel, Samson M. and Zhai, Kevin and Al-Ishaq, Raghad Khalid and Abotaleb, Mariam and Nosal, Vladimir and Kajo, Karol and Ashrafizadeh, Milad and Zarrabi, Ali and Brockmueller, Aranka and Shakibaei, Mehdi and Sabaka, Peter and Mozos, Ioana and Ullrich, David and Prosecky, Robert and La Rocca, Giampiero and Caprnda, Martin and Büsselberg, Dietrich and Rodrigo, Luis and Kruzliak, Peter and Kubatka, Peter (2021) Flavonoids against the SARS-CoV-2 induced inflammatory storm. Biomedicine and Pharmacotherapy, 138 . ISSN 0753-3322 (Print) 1950-6007 (Online)

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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 (3CLpro) 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 flavonoids in the management of COVID-19 and also points to the multiple biological effects of flavonoids on signaling pathways associated with the inflammation processes that are deregulated in the pathology induced by SARS-CoV-2. The identification of agents, including naturally occurring substances such as flavonoids, represents great approach potentially utilizable in the management of COVID-19. Although not clinically investigated yet, the applicability of flavonoids against COVID-19 could be a promising strategy due to a broad spectrum of their biological activities.
Item Type: Article
Uncontrolled Keywords: Anti-inflammatory effects; COVID-19; Cytokine storm; Flavonoids; Immunomodulation; Inflammation; Phytochemicals; SARS-CoV-2
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Sabancı University Nanotechnology Research and Application Center
Depositing User: Ali Zarrabi
Date Deposited: 18 Aug 2022 13:41
Last Modified: 18 Aug 2022 13:41
URI: https://research.sabanciuniv.edu/id/eprint/43317

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