id author title date pages extension mime words sentences flesch summary cache txt cord-317523-idji1l0a Xu, Huanzhou SARS-CoV-2 viroporin triggers the NLRP3 inflammatory pathway 2020-10-27 .txt text/plain 1192 59 42 With the selective NLRP3 inhibitor MCC950 able to block ORF3a-mediated inflammasome activation and key ORF3a residues needed for virus release and inflammasome activation conserved in SARS-CoV-2 isolates across continents, ORF3a and NLRP3 present prime targets for intervention. In a pared-down system, we investigate the influence of ORF3a, an essential SARS-CoV-2 protein, on the inflammatory machinery and find that it activates NLRP3, the most prominent inflammasome by causing potassium loss across the cell membrane. To assess if ORF3a also 135 mediates activation of other prominent inflammasomes including NLRP1 and NLRC4, we 136 depleted each of these molecules but were unable to block cleavage of pro-caspase 1 (Fig.2G) , 137 indicating that ORF3a predominantly activates the NLRP3 inflammasome. In summary, an essential viroporin required for release of SARS-CoV-2 from infected cells is also 178 able to prime and activate the NLRP3 inflammasome, the machinery responsible for much of the ./cache/cord-317523-idji1l0a.txt ./txt/cord-317523-idji1l0a.txt