Investigating the Nexus of NLRP3 Inflammasomes and COVID-19 Pathogenesis: Unraveling Molecular Triggers and Therapeutic Strategies
Abstract
:1. Introduction
2. Activation of NLRP3
3. Functions of NLRP3 Inflammasome in SARS-CoV-2 Infection
3.1. Findings in the Context of SARS-CoV-2 Infection
3.2. The Activation of NLRP3 by SARS-CoV-2 Proteins
3.3. Role of NLRP3 Inflammasome in COVID-19 Immune Activation
3.4. Effect of NLRP3 on Cytokine Storms in SARS-CoV-2 Infection
3.5. NLRP3’s Role in SARS-CoV-2-Induced Multiorgan Dysfunctions
3.6. The Role of Key Pro-Inflammatory Factors IL-18 and IL-1β Downstream of NLRP3 in SARS-CoV-2 Infection
4. Compounds Targeting NLRP3 in the Treatment of SARS-CoV-2 Infection
4.1. Synthetic Compounds
4.1.1. Alkenyl Sulfonylurea Derivative 7
4.1.2. Chloroquine and Hydroxychloroquine
4.1.3. Dexamethasone
4.1.4. DFV890
4.1.5. MCC950
4.2. Immunomodulator Drugs
25-HC@DDAB
4.3. Antidiabetic Drugs
Metformin
4.4. Lipid-Lowering Drugs
Statins
4.5. Natural Products
4.5.1. Colchicine
4.5.2. Curcumin
5. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drugs | Drug Category | The Role and Mechanism in the Treatment of COVID-19 | References |
---|---|---|---|
Alkenyl sulfonylurea derivative 7 | Synthetic compounds | It blocked the oligomerization of ASC during NLRP3 activation, and inhibited IL-1 β and IL-18 in a dose-dependent manner. | [59] |
Chloroquine/ Hydroxychloroquine | Synthetic compounds | Chloroquine decreased the activity of NF-κB and MAPK, and inhibited the activation of caspase-1 and the formation of ASC complex. | [60,61] |
Dexamethasone | Synthetic compounds | Reduce the release of pro-inflammatory factors and slightly regulate the protein level of NLRP3. | [62,63] |
DFV890 | Synthetic compounds | Inhibit the activity of NLRP3 by directly binding to NLRP3 and locking the protein in an inactive conformation. | [64,65] |
MCC950 | Synthetic compounds | Inhibit the activation of NLRP3 pathway and reduce the release of pro-inflammatory cytokines. | [22,66,67] |
25-HC@DDAB | Immunomodulator drugs | Down-regulate NF-κB and SREBP2 signal pathways in PBMC derived from COVID-19 patients and reduce the expression of NLRP3 gene. | [68] |
Metformin | Antidiabetic drugs | Inhibition of TLR-induced mitochondrial DNA synthesis, thereby blocking the activation of NLRP3 inflammatory bodies in vivo and in vitro. | [69,70] |
Statins | Lipid-lowering drugs | Blocking NF-κB and NLRP3 inflammatory bodies. | [71] |
Colchicine | Natural products | Inhibition of P2X7 receptor reduces the formation of inflammatory bodies in NLRP3. | [72] |
Curcumin | Natural products | Inhibit the activity of NLRP3. | [73,74,75] |
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He, Q.; Hu, D.; Zheng, F.; Chen, W.; Hu, K.; Liu, J.; Yao, C.; Li, H.; Wei, Y. Investigating the Nexus of NLRP3 Inflammasomes and COVID-19 Pathogenesis: Unraveling Molecular Triggers and Therapeutic Strategies. Viruses 2024, 16, 213. https://doi.org/10.3390/v16020213
He Q, Hu D, Zheng F, Chen W, Hu K, Liu J, Yao C, Li H, Wei Y. Investigating the Nexus of NLRP3 Inflammasomes and COVID-19 Pathogenesis: Unraveling Molecular Triggers and Therapeutic Strategies. Viruses. 2024; 16(2):213. https://doi.org/10.3390/v16020213
Chicago/Turabian StyleHe, Qun, Da Hu, Fuqiang Zheng, Wenxuan Chen, Kanghong Hu, Jinbiao Liu, Chenguang Yao, Hanluo Li, and Yanhong Wei. 2024. "Investigating the Nexus of NLRP3 Inflammasomes and COVID-19 Pathogenesis: Unraveling Molecular Triggers and Therapeutic Strategies" Viruses 16, no. 2: 213. https://doi.org/10.3390/v16020213
APA StyleHe, Q., Hu, D., Zheng, F., Chen, W., Hu, K., Liu, J., Yao, C., Li, H., & Wei, Y. (2024). Investigating the Nexus of NLRP3 Inflammasomes and COVID-19 Pathogenesis: Unraveling Molecular Triggers and Therapeutic Strategies. Viruses, 16(2), 213. https://doi.org/10.3390/v16020213