SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation

Abstract Excessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to also COVID-19 severity. Here, we show a distinct mechanism by which N protein promotes NLRP3 inflammasome activation induce hyperinflammation. facilitates maturation proinflammatory cytokines and induces cultured cells mice. Mechanistically, interacts directly protein, the binding ASC, assembly. More importantly, aggravates lung injury, accelerates death sepsis acute inflammation mouse models, IL-1? IL-6 Notably, N-induced injury cytokine production blocked MCC950 (a specific inhibitor NLRP3) Ac-YVAD-cmk (an caspase-1). Therefore, this study reveals excessive responses.