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

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.

Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement

“…These proteins induce various cellular pro-inflammatory stress processes, including autophagy, oxidative and mitochondrial stress, and endoplasmic reticulum stress (ERS) [ 40 , 41 , 42 ]. Furthermore, SARS-CoV-2, including through the effects of its structural proteins S, E, and N, can induce pro-inflammatory cellular stress in various cell types via activation of the NLRP3 inflammasome [ 43 , 44 , 45 ]. Gastrointestinal Impact and Microbiome Disruption: The long-term persistence of SARS-CoV-2 as potential bacteriophages in the intestinal microflora and the sustained disruption of the intestinal microbiome in LC have been demonstrated.…”

“…These proteins induce various cellular pro-inflammatory stress processes, including autophagy, oxidative and mitochondrial stress, and endoplasmic reticulum stress (ERS) [ 40 , 41 , 42 ]. Furthermore, SARS-CoV-2, including through the effects of its structural proteins S, E, and N, can induce pro-inflammatory cellular stress in various cell types via activation of the NLRP3 inflammasome [ 43 , 44 , 45 ].…”