Pervasive aggregation and depletion of host and viral proteins in response to cysteine-reactive electrophilic compounds.

ABSTRACT: Protein homeostasis is tightly regulated, with damaged or misfolded proteins quickly eliminated by the proteasome and autophagosome pathways. By co-opting these processes, targeted protein degradation technologies enable pharmacological manipulation of protein abundance. Recently, cysteine-reactive molecules have been added to the degrader toolbox, which offer the benefit of unlocking the therapeutic potential of 'undruggable' protein targets. The proteome-wide impact of these molecules remains to be fully understood and given the general reactivity of many classes of cysteine-reactive electrophiles, on- and off-target effects are likely. Using chemical proteomics, we identified a cysteine-reactive small molecule degrader of the SARS-CoV-2 nonstructural protein 14 (nsp14), which effects de

SUBMITTER: Julio AR 

PROVIDER: S-EPMC10680658 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature