Ethidium-based Derivatives as HIV-1 Rev-RRE Inhibitors

Katy Muzikar
University of California, San Diego

Anti-HIV therapy which targets viral RNA sites instead of mature proteins is a crucial subject of study, as resistant HIV-variants are rapidly appearing. The goal of this project is to develop anti-viral agents that selectively target the HIV-1 Rev Response Element (RRE) and interfere with Rev binding. The binding of the Rev protein to its cognate RNA site, the RRE, is responsible for the export of unspliced and singly spliced HIV genomic RNA out of the host cell's nucleus, a crucial element of the viral life cycle. Successful inhibition of Rev-RRE binding should therefore halt HIV replication. As ethidium-based derivatives have recently been found to exhibit high affinity to the RRE, this project aims to synthesize modified ethidium-based intercalators and examine their affinity and selectivity to the RRE using fluorescence-based binding assays. The poster will present the synthetic routes employed to create these derivatives as well as the evaluation of their RRE binding.