Kiira Ratia

TL;DR: The identification and characterization of a 316-amino-acid catalytic core domain of PLpro that can efficiently cleave replicase substrates in trans-cleavage assays and peptide substrate in fluorescent resonance energy transfer-based protease assays is reported.

TL;DR: Findings provide proof-of-principle that PLpro is a viable target for development of antivirals directed against SARS-CoV, and that potent noncovalent cysteine protease inhibitors can be developed with specificity directed toward pathogenic deubiquitinating enzymes without inhibiting host DUBs.

TL;DR: This work describes the 1.85-A crystal structure of the catalytic core of SARS-CoV PLpro and shows that the overall architecture adopts a fold closely resembling that of known deubiquitinating enzymes.

TL;DR: This study focuses on the SARS-CoV papain-like protease (PLP), which engages and antagonizes the IFN induction and NF-κB signaling pathways, and shows that the ubiquitin-like domain of PLP is necessary for pathway antagonism but not sufficient by itself to block these pathways regardless of the enzymatic activity of the protease.

TL;DR: The results indicated that a component of coronavirus PLP-mediated interferon antagonism was independent of protease and DUB activity, and suggest that these independent activities may provide multiple targets for antiviral therapies.