In crystallo-screening for discovery of human norovirus 3C-like protease inhibitors.

ABSTRACT: Outbreaks of human epidemic nonbacterial gastroenteritis are mainly caused by noroviruses. Viral replication requires a 3C-like cysteine protease (3CL^pro) which processes the 200 kDa viral polyprotein into six functional proteins. The 3CL^pro has attracted much interest due to its potential as a target for antiviral drugs. A system for growing high-quality crystals of native Southampton norovirus 3CL^pro (SV3CP) has been established, allowing the ligand-free crystal structure to be determined to 1.3 Å in a tetrameric state. This also allowed crystal-based fragment screening to be performed with various compound libraries, ultimately to guide drug discovery for SV3CP. A total of 19 fragments were found to bind to the protease out of the 844 which were screened

SUBMITTER: Guo J 

PROVIDER: S-EPMC7365090 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature