Flavonoids as potential phytotherapeutics to combat cytokine storm in <scp>SARS‐CoV</scp>‐2

Gour, Abhishek; Manhas, Diksha; Bag, Swarnendu; Gorain, Bapi; Nandi, Utpal

doi:10.1002/ptr.7092

Cited by 44 publications

(34 citation statements)

References 296 publications

(375 reference statements)

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“…Certain natural flavonoids [184] have been proposed as prophylaxis or treatment against COVID-19 [185][186][187][188][189]. Such flavonoids are found in green plants and seeds and possess potent anti-oxidant, anti-inflammatory, and cytoprotective properties [184].…”

Section: Discussionmentioning

confidence: 99%

Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome?

2022

Mol Neurobiol

111

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SARS-CoV-2 infects cells via its spike protein binding to its surface receptor on target cells and results in acute symptoms involving especially the lungs known as COVID-19. However, increasing evidence indicates that many patients develop a chronic condition characterized by fatigue and neuropsychiatric symptoms, termed long-COVID. Most of the vaccines produced so far for COVID-19 direct mammalian cells via either mRNA or an adenovirus vector to express the spike protein, or administer recombinant spike protein, which is recognized by the immune system leading to the production of neutralizing antibodies. Recent publications provide new findings that may help decipher the pathogenesis of long-COVID. One paper reported perivascular inflammation in brains of deceased patients with COVID-19, while others showed that the spike protein could damage the endothelium in an animal model, that it could disrupt an in vitro model of the blood-brain barrier (BBB), and that it can cross the BBB resulting in perivascular inflammation. Moreover, the spike protein appears to share antigenic epitopes with human molecular chaperons resulting in autoimmunity and can activate toll-like receptors (TLRs), leading to release of inflammatory cytokines. Moreover, some antibodies produced against the spike protein may not be neutralizing, but may change its conformation rendering it more likely to bind to its receptor. As a result, one wonders whether the spike protein entering the brain or being expressed by brain cells could activate microglia, alone or together with inflammatory cytokines, since protective antibodies could not cross the BBB, leading to neuro-inflammation and contributing to long-COVID. Hence, there is urgent need to better understand the neurotoxic effects of the spike protein and to consider possible interventions to mitigate spike proteinrelated detrimental effects to the brain, possibly via use of small natural molecules, especially the flavonoids luteolin and quercetin. KeywordsACE2 • Antibodies • Blood-brain barrier • Brain • Coronavirus • Endothelial cells • Receptor • Spike protein

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Section: Discussionmentioning

confidence: 99%

Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome?

2022

Mol Neurobiol

111

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“…Among these 10 drugs, the cytotoxic drugs chromium (III) chloride and irinotecan hydrochloride should not be considered as candidates. Antimycin A ( 52 ), proscillaridin ( 53 , 54 ), troglitazone ( 55 , 56 ), thapsigargin ( 57 , 58 ), genistein ( 59 , 60 ), and testosterone ( 61 ) were considered as potential drugs for COVID-19 in previous studies. Acetovanillone and hyperforin have not been studied for the treatment of COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms of Cardiac Injury Associated With Myocardial SARS-CoV-2 Infection

Lou

Zhou

2022

Front. Cardiovasc. Med.

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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world. The development of cardiac injury is a common condition in patients with COVID-19, but the pathogenesis remains unclear. The RNA-Seq dataset (GSE150392) comparing expression profiling of mock human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and SARS-CoV-2-infected hiPSC-CMs was obtained from Gene Expression Omnibus (GEO). We identified 1,554 differentially expressed genes (DEGs) based on GSE150392. Gene set enrichment analysis (GSEA), Gene ontology (GO) analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that immune-inflammatory responses were activated by SARS-CoV-2, while muscle contraction, cellular respiration, and cell cycle of hiPSC-CMs were inhibited. A total of 15 hub genes were identified according to protein–protein interaction (PPI), among which 11 upregulated genes were mainly involved in cytokine activation related to the excessive inflammatory response. Moreover, we identified potential drugs based on these hub genes. In conclusion, SARS-CoV-2 infection of cardiomyocytes caused a strong defensive response, leading to excessive immune inflammation, cell hypoxia, functional contractility reduction, and apoptosis, ultimately resulting in myocardial injury.

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“…Additionally, there are some recently-published review articles that have focused on the effect of flavonoids on one specific target (e.g., ACE-2) or clinical manifestation (cytokine storms or lung injury) of SARS-CoV-2 infection [ 124 , 125 , 126 , 127 ]. Such points of view can put a focus on the development of natural medicines against one specific viral target; however, we preferred a more general approach in our study.…”

Section: Discussionmentioning

confidence: 99%

Flavonoids as Promising Antiviral Agents against SARS-CoV-2 Infection: A Mechanistic Review

et al. 2021

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A newly diagnosed coronavirus in 2019 (COVID-19) has affected all human activities since its discovery. Flavonoids commonly found in the human diet have attracted a lot of attention due to their remarkable biological activities. This paper provides a comprehensive review of the benefits of flavonoids in COVID-19 disease. Previously-reported effects of flavonoids on five RNA viruses with similar clinical manifestations and/or pharmacological treatments, including influenza, human immunodeficiency virus (HIV), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola, were considered. Flavonoids act via direct antiviral properties, where they inhibit different stages of the virus infective cycle and indirect effects when they modulate host responses to viral infection and subsequent complications. Flavonoids have shown antiviral activity via inhibition of viral protease, RNA polymerase, and mRNA, virus replication, and infectivity. The compounds were also effective for the regulation of interferons, pro-inflammatory cytokines, and sub-cellular inflammatory pathways such as nuclear factor-κB and Jun N-terminal kinases. Baicalin, quercetin and its derivatives, hesperidin, and catechins are the most studied flavonoids in this regard. In conclusion, dietary flavonoids are promising treatment options against COVID-19 infection; however, future investigations are recommended to assess the antiviral properties of these compounds on this disease.

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Flavonoids as potential phytotherapeutics to combat cytokine storm in SARS‐CoV‐2

Cited by 44 publications

References 296 publications

Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome?

Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome?

Molecular Mechanisms of Cardiac Injury Associated With Myocardial SARS-CoV-2 Infection

Flavonoids as Promising Antiviral Agents against SARS-CoV-2 Infection: A Mechanistic Review

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