Graphical abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical presentations, ranging from asymptomatic cases to severe pneumonia or even death. In severe COVID-19 cases, an increased level of proinflammatory cytokines has been observed in the bloodstream, forming the so-called “cytokine storm”. Generally, nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation intensely induces cytokine production as an inflammatory response to viral infection. Therefore, the NLRP3 inflammasome can be a potential target for the treatment of COVID-19. Hence, this review first introduces the canonical NLRP3 inflammasome activation pathway. Second, we review the cellular/molecular mechanisms of NLRP3 inflammasome activation by SARS-CoV-2 infection (e.g., viroporins, ion flux and the complement cascade). Furthermore, we describe the involvement of the NLRP3 inflammasome in the pathogenesis of COVID-19 (e.g., cytokine storm, respiratory manifestations, cardiovascular comorbidity and neurological symptoms). Finally, we also propose several promising inhibitors targeting the NLRP3 inflammasome, cytokine products and neutrophils to provide novel therapeutic strategies for COVID-19.
【저자키워드】 COVID-19, SARS-CoV-2, Pathogenesis, COVID-19, Coronavirus disease 2019, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, ACE2, angiotensin-converting enzyme 2, TMPRSS2, Transmembrane serine protease 2, IFN, interferon, inhibitor, ARDS, acute respiratory distress syndrome, CNS, Central Nervous System, TNF, Tumor Necrosis Factor, NETs, neutrophil extracellular traps, Ang II, Angiotensin II, LDH, lactate dehydrogenase, NF-κB, Nuclear Factor kappa B, ROS, reactive oxygen species, PAMPs, pathogen-associated molecular patterns, ALI, Acute Lung Injury, LPS, lipopolysaccharide, BBB, blood-brain barrier, ERK, extracellular signal-regulated kinase, ERGIC, endoplasmic reticulum-Golgi apparatus intermediate compartment, NLRP3, nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3, S/M/N/E protein, spike/membrane/nucleocapsid/envelope protein, ORF3a/8a/8b, open reading frame 3a/8a/8b, IL-18/1β/6/8/10/1RA, interleukin-18/1β/6/8/10/1RA, ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain, LRR, , leucine-rich repeat, PYD, pyrin domain, CARD, caspase recruitment domain, DAMPs, damage-associated molecular patterns, PKR, double-stranded RNA-dependent protein kinase, NEK7, never in mitosis A-related kinase 7, mtDNA, mitochondrial DNA, AT1R, Ang II type 1 receptor, MBL, mannan-binding lectin, MASP2, MBL-associated serine protease 2, MAC, membrane attack complex, P2 × 7, P2X purinergic receptor 7, MEK, mitogen-activated protein kinase, CXCL10, C-X-C motif chemokine ligand 10, MERS-CoV, middle east respiratory syndrome coronavirusus, NLRP3 inflammasomeome,