Emerging role of IL-6 and NLRP3 inflammasome as potential therapeutic targets to combat COVID-19: Role of lncRNAs in cytokine storm modulation

Paniri, Alireza; Akhavan‐Niaki, Haleh

doi:10.1016/j.lfs.2020.118114

Cited by 69 publications

(73 citation statements)

References 145 publications

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“…IL-6 is known for downstream target of IL-1β, consequently activated and increased in patients with NLRP3 inflammasome related diseases 9 . Recently, it has been reported that IL-6 and NLRP3 inflammasome are main regulator in immune response stimulated by pathogen and viral infection such as SARS-CoV-2 10 . Additionally, TNF-α also has a function on the activation of NLRP3 inflammasome components in inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

Fucoxanthin from microalgae Phaeodactylum tricornutum inhibits pro-inflammatory cytokines by regulating both NF-κB and NLRP3 inflammasome activation

Lee

Shin

Park

et al. 2021

Sci Rep

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Pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α are mediated by the activation of various kinds of signaling pathways in the innate immune system. Particularly, NF-κB and NLRP3 inflammasome signaling are involved in the production and secretion of these cytokines. Each signaling is participated in the two steps necessary for IL-1β, a representative pro-inflammatory cytokine, to be processed into a form secreted by cells. In the priming step stimulated by LPS, pro-IL-1β is synthesized through NF-κB activation. Pro-IL-1β cleavages into mature IL-1β by formed NLRP3 inflammasome in the activation step induced by ATP. The mature form of IL-1β is subsequently secreted out of the cell, causing inflammation. Moreover, IL-6 and TNF-α are known to increase in NLRP3 inflammasome-mediated conditions. Here, we found that fucoxanthin, one of the major components of Phaeodactylum tricornutum, has an inhibitory effect on NF-κB and NLRP3 inflammasome activation induced by the combination of LPS and ATP in bone marrow-derived immune cells as well as astrocytes. Fucoxanthin, which is abundant in the EtOH fraction of Phaeodactylum tricornutum extracts, has shown to have less cell toxicity and found to decrease the production of major pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Fucoxanthin has also shown to suppress the expression of cleaved caspase-1 and the oligomerization of ASC, which are the main components of the NLRP3 inflammasome. Furthermore, phosphorylated IκBα and pro-IL-1β expression decreased in the presence of fucoxanthin, suggesting that fucoxanthin can negatively regulate the priming step of inflammasome signaling. Thus, our results provide reliable evidence that fucoxanthin may serve as a key candidate in the development of potential therapeutic agents for inflammatory diseases as well as neurodegenerative diseases caused by NF-κB and NLRP3 inflammasome activation.

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Section: Introductionmentioning

confidence: 99%

Fucoxanthin from microalgae Phaeodactylum tricornutum inhibits pro-inflammatory cytokines by regulating both NF-κB and NLRP3 inflammasome activation

Lee

Shin

Park

et al. 2021

Sci Rep

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“…In addition, Paniri et al. [ 54 ] proposed that glyburide might be a useful drug to combat SARS-CoV-2 by blocking the wide spectrum of molecules related to inflammatory cascade. Certainly, these in silico predictions will require the in vitro target validation experiments in the future.…”

Section: Resultsmentioning

confidence: 99%

MCCS: a novel recognition pattern-based method for fast track discovery of anti-SARS-CoV-2 drugs

Feng

Chen

Xue

et al. 2020

Briefings in Bioinformatics

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Given the scale and rapid spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, or 2019-nCoV), there is an urgent need to identify therapeutics that are effective against COVID-19 before vaccines are available. Since the current rate of SARS-CoV-2 knowledge acquisition via traditional research methods is not sufficient to match the rapid spread of the virus, novel strategies of drug discovery for SARS-CoV-2 infection are required. Structure-based virtual screening for example relies primarily on docking scores and does not take the importance of key residues into consideration, which may lead to a significantly higher incidence rate of false-positive results. Our novel in silico approach, which overcomes these limitations, can be utilized to quickly evaluate FDA-approved drugs for repurposing and combination, as well as designing new chemical agents with therapeutic potential for COVID-19. As a result, anti-HIV or antiviral drugs (lopinavir, tenofovir disoproxil, fosamprenavir and ganciclovir), antiflu drugs (peramivir and zanamivir) and an anti-HCV drug (sofosbuvir) are predicted to bind to 3CLPro in SARS-CoV-2 with therapeutic potential for COVID-19 infection by our new protocol. In addition, we also propose three antidiabetic drugs (acarbose, glyburide and tolazamide) for the potential treatment of COVID-19. Finally, we apply our new virus chemogenomics knowledgebase platform with the integrated machine-learning computing algorithms to identify the potential drug combinations (e.g. remdesivir+chloroquine), which are congruent with ongoing clinical trials. In addition, another 10 compounds from CAS COVID-19 antiviral candidate compounds dataset are also suggested by Molecular Complex Characterizing System with potential treatment for COVID-19. Our work provides a novel strategy for the repurposing and combinations of drugs in the market and for prediction of chemical candidates with anti-COVID-19 potential.

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“…The NLRP3 inflammasome is a critical cytosolic protein complex responsible for both acute and chronic inflammation in response to various pathogens 27 , including SARS-CoV-2. 28 , 29 Anti-inflammatory diets are associated with improved pulmonary function in non-asthmatic Hispanic adults 30 and improved lung function and lower mortality in individuals with COPD. 31 Anti-inflammatory diets emphasize the inclusion of herbs and spices which have known antioxidant and anti-inflammatory effects and may slow the progression of COPD in which NLRP3 inflammasome activation plays a critical pathogenic role.…”

Section: Dietmentioning

confidence: 99%

Integrative medicine considerations for convalescence from mild-to-moderate COVID-19 disease

Alschuler

Chiasson

Horwitz

et al. 2022

EXPLORE

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The majority of individuals infected with SARS-CoV-2 have mild-to-moderate COVID-19 disease. Convalescence from mild-to-moderate (MtoM) COVID-19 disease may be supported by integrative medicine strategies. Integrative Medicine (IM) is defined as healing-oriented medicine that takes account of the whole person, including all aspects of lifestyle. Integrative medicine strategies that may support recovery from MtoM COVID-19 are proposed given their clinically studied effects in related conditions. Adoption of an anti-inflammatory diet, supplementation with vitamin D, glutathione, melatonin, Cordyceps, Astragalus and garlic have potential utility. Osteopathic manipulation, Qigong, breathing exercises and aerobic exercise may support pulmonary recovery. Stress reduction, environmental optimization, creative expression and aromatherapy can provide healing support and minimize enduring trauma. These modalities would benefit from clinical trials in people recovering from COVID-19 infection.

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Emerging role of IL-6 and NLRP3 inflammasome as potential therapeutic targets to combat COVID-19: Role of lncRNAs in cytokine storm modulation

Cited by 69 publications

References 145 publications

Fucoxanthin from microalgae Phaeodactylum tricornutum inhibits pro-inflammatory cytokines by regulating both NF-κB and NLRP3 inflammasome activation

Fucoxanthin from microalgae Phaeodactylum tricornutum inhibits pro-inflammatory cytokines by regulating both NF-κB and NLRP3 inflammasome activation

MCCS: a novel recognition pattern-based method for fast track discovery of anti-SARS-CoV-2 drugs

Integrative medicine considerations for convalescence from mild-to-moderate COVID-19 disease

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