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Investigating the Nexus of NLRP3 Inflammasomes and COVID-19 Pathogenesis: Unraveling Molecular Triggers and Therapeutic Strategies - PubMed Skip to main page content
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Review
. 2024 Jan 31;16(2):213.
doi: 10.3390/v16020213.

Investigating the Nexus of NLRP3 Inflammasomes and COVID-19 Pathogenesis: Unraveling Molecular Triggers and Therapeutic Strategies

Qun He  1 , Da Hu  2 , Fuqiang Zheng  1 , Wenxuan Chen  1 , Kanghong Hu  1 , Jinbiao Liu  1 , Chenguang Yao  1 , Hanluo Li  1 , Yanhong Wei  1
Affiliations
Review

Investigating the Nexus of NLRP3 Inflammasomes and COVID-19 Pathogenesis: Unraveling Molecular Triggers and Therapeutic Strategies

Qun He et al. Viruses. .

Abstract

The coronavirus disease 2019 (COVID-19) global pandemic, caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been marked by severe cases demonstrating a "cytokine storm", an upsurge of pro-inflammatory cytokines in the bloodstream. NLRP3 inflammasomes, integral to the innate immune system, are speculated to be activated by SARS-CoV-2 within host cells. This review investigates the potential correlation between NLRP3 inflammasomes and COVID-19, exploring the cellular and molecular mechanisms through which SARS-CoV-2 triggers their activation. Furthermore, promising strategies targeting NLRP3 inflammasomes are proposed to mitigate the excessive inflammatory response provoked by SARS-CoV-2 infection. By synthesizing existing studies, this paper offers insights into NLRP3 as a therapeutic target, elucidating the interplay between COVID-19 and its pathophysiology. It serves as a valuable reference for future clinical approaches in addressing COVID-19 by targeting NLRP3, thus providing potential avenues for therapeutic intervention.

Keywords: COVID-19; NLRP3 inflammasome; SARS-CoV-2; cytokine storm; therapeutic targets.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. Da Hu, as an employee of Sinopharm Animal Health Corporation Ltd, participated in the early writing work, and Da Hu stated that there was no business relationship or economic interest with the company that might constitute a conflict of interest.

Figures

Figure 1
Figure 1
NLRP3 inflammasome activation pathway. Initiation: stimulation of the membrane receptor TLR by damage-associated molecular patterns (DAMPs) initiates NF-κB translocation, inducing the upregulation of components associated with the NLRP3 inflammasome. Activation: key cellular signals triggered by activated NLRP3 include potassium (K+) efflux, calcium (Ca2+) efflux, reactive oxygen species (ROS) production, mitochondrial impairment, and lysosome destabilization. Activated NLRP3 catalyzes procaspase-1, leading to the cleavage of procaspase-1 into active caspase-1. Caspase-1 then cleaves pro-IL-1β and pro-IL-18 into their active forms. Additionally, GSDMD cleavage by caspase-1 facilitates the release of IL-1β and IL-18.
Figure 2
Figure 2
NLRP3’s role in SARS-CoV-2-induced multiorgan dysfunctions.
Figure 3
Figure 3
Compound targeting NLRP3 inhibits cytokine storm induced by SARS-CoV-2 infection. SARS-CoV-2 infection triggers activation of NLRP3 inflammasomes, leading to the accumulation and activation of immune cells. This provokes rapid migration of immune cells to infected sites, triggering inflammatory responses in lungs and other tissues, exacerbating the disease, and releasing inflammatory mediators such as IL-1β, IL-18, TNF-α, and IFN-γ, culminating in cytokine storms. Compounds targeting NLRP3 can mitigate SARS-CoV-2-induced inflammation by inhibiting the activation of NLRP3 inflammasomes. Representative NLRP3 inhibitors are depicted in the figure.
See this image and copyright information in PMC

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