Destabilization of the human RED-SMU1 splicing complex as a basis for host-directed antiinfluenza strategy.

ABSTRACT: New therapeutic strategies targeting influenza are actively sought due to limitations in current drugs available. Host-directed therapy is an emerging concept to target host functions involved in pathogen life cycles and/or pathogenesis, rather than pathogen components themselves. From this perspective, we focused on an essential host partner of influenza viruses, the RED-SMU1 splicing complex. Here, we identified two synthetic molecules targeting an α-helix/groove interface essential for RED-SMU1 complex assembly. We solved the structure of the SMU1 N-terminal domain in complex with RED or bound to one of the molecules identified to disrupt this complex. We show that these compounds inhibiting RED-SMU1 interaction also decrease endogenous RED-SMU1 levels and inhibit viral mRNA splicing an

SUBMITTER: Ashraf U 

PROVIDER: S-EPMC6561211 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature