Fig. 3
The pyroptosis pathway in SARS-CoV-2 infection. SARS‐CoV‐2 S triggers NLRP3 inflammasome activation to release the pro‐inflammatory cytokine IL‐1β. SARS-CoV-2 NSP6 stimulates the activation of the NLRP3 inflammasome by interacting with ATP6AP1, a vacuolar ATPase proton pump component. SARS-CoV-2 ORF3a and N facilitated NLRP3 inflammasome assembly induces ASC speck formation. In addition, SARS-CoV-2 N protein can protect GSDMD from caspase-1 cleavage. Moreover, SARS-CoV-2 N, NSP6, and ORF7a promote activation of the NF-κB pathway via interactions with TAK1 and IKK complexes, which stimulate pro-inflammatory cytokine production, containing pro-IL-1 β, pro-IL-18, procaspase-1, and NLRP3, which leads to pyroptosis. SARS-CoV-2 E can activate the NLRP3-dependent inflammasome and TLR2 pathways to trigger pro-inflammatory cytokines through activation of the NF-κB pathway. Additionally, SARS-CoV-2 E activates the NLRP3-dependent inflammasome and TLR2 pathways and forms a cation channel to trigger rapid cell death. SARS-CoV-2 NSP1 and NSP13 hinder the pyroptosis of infected cells by inhibiting the activity of caspase-1
