Synthesis, Activity and Structure-Activity Relationship of Noroviral Protease Inhibitors.

The protease of norovirus, an important human pathogen, is essential for the viral replication and, therefore, represents a potential drug target. A series of tripeptide-based inhibitors of the protease were designed, synthesized and tested, among which several potent inhibitors were identified with Ki values as low as 75 nM. The structure-activity relationships of these inhibitors are discussed.