Dengue virus and West Nile virus protease inhibitors

Abstract

Dengue virus and West Nile virus are important mosquito-borne pathogens of Flaviviridae family affecting millions of people worldwide and causing a severe global healthcare threat. However, currently there are no approved effective antiviral drugs or vaccines available for the treatment of virus infection. This thesis describes the design, synthesis and discovery of two novel classes of reversible competitive inhibitors of Dengue Virus and West Nile Virus NS2B/NS3 protease. Structure-activity relationship studies have led to the identification of a low micromolar hit, which will be used in a hit-to-lead campaign to generate lead compounds that display superior ADMET and PK characteristics.