Advancement of antiviral inhibitors of chikungunya virus

PROJECT SUMMARY Novel therapies for the treatment of chikungunya virus (CHIKV) infections are urgently needed to address the alarming spread of this pathogen across the Americas. We have identified three distinct series of potent, selective, and orally bioavailable inhibitors of CHIKV replication. In this Phase II renewal SBIR project, we will optimize these series of CHIKV inhibitors to Pre-Development stage and advance a first ever CHIKV antiviral candidate to IND-enabling studies. To accomplish this task, we will execute an integrated medicinal chemistry optimization/biological profiling campaign to optimize the potency, drug-like properties and oral exposure of each series. One or more Pre-Development Candidates will be identified and advanced through candidate selection studies into non-GLP repeat-dose tox in both rats and dogs.PROJECT NARRATIVE The chikungunya virus (CHIKV) epidemic that started in 2014 has continued to be a major health issue in the Americas resulting in over 2 million infections. Morbidity associated with CHIKV infection includes severe, debilitating arthralgia (joint pain) that can persist for years. There are no antiviral agents or vaccines approved for CHIKV treatment or prevention. Here, we propose to optimize three lead series of CHIKV inhibitors to Pre- Development stage and position a Development Candidate for IND-enabling studies.