Selective AAK1 and GAK Inhibitors for Combating Dengue and Other Emerging Viral Infections
Abstract
Emerging viruses, such as dengue (DENV) and Ebola (EBOV), pose threats to military and global health. There are no approved drugs or vaccines available against these viruses. Our goal is to develop broad-spectrum antivirals with a high genetic barrier to resistance by targeting host proteins that are critical to the life cycle of multiple viruses. The goals of this project are to optimize selective inhibitors of AAK1 and GAK, host kinases we discovered as targets for broad-spectrum antivirals, and advance their development to a pre-IND stage. This approach would also protect against multiple other biothreat agents. During the past year we have continued to optimize our inhibitors. Our promising AAK1 and GAK inhibitors have broad spectrum activity (DENV, EBOV and CHIKV). Effort to enhance their PK and advance them to in vivo experiments are ongoing. We have generated a series of derivatives of AAK1 inhibitors based on the Azaindole series with several hits showing promising antiviral activity. We have also demonstrated synergy between AAK1 and GAK inhibitors and a high barrier to resistance in mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1086354
Entities
People
- Jennifer M. Brannan
- Raul Andino
- Shirit Einav
- Steven De Jonghe
Organizations
- Stanford University School of Medicine