A conformational switch high-throughput screening assay and allosteric inhibition of the flavivirus NS2B-NS3 protease.

ABSTRACT: The flavivirus genome encodes a single polyprotein precursor requiring multiple cleavages by host and viral proteases in order to produce the individual proteins that constitute an infectious virion. Previous studies have revealed that the NS2B cofactor of the viral NS2B-NS3 heterocomplex protease displays a conformational dynamic between active and inactive states. Here, we developed a conformational switch assay based on split luciferase complementation (SLC) to monitor the conformational change of NS2B and to characterize candidate allosteric inhibitors. Binding of an active-site inhibitor to the protease resulted in a conformational change of NS2B and led to significant SLC enhancement. Mutagenesis of key residues at an allosteric site abolished this induced conformational change and S

SUBMITTER: Brecher M 

PROVIDER: S-EPMC5462475 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature