Structure-based design of stapled peptides to target Gag-Pol and INI1 interaction to block assembly

Project Narrative: Despite advances in the treatment of HIV-1 infection, the AIDS pandemic remains unabated and warrants the continued development of novel anti-HIV-1 therapeutics. Host-Virus Protein/protein interactions (PPI) are viable therapeutic targets to develop novel anti-viral reagents. Based on the newly discovered structure of INI1, an HIV-1 integrase binding host protein, and based on the novel insights obtained of INI1’s molecular mimicry to HIV-1 TAR RNA, we propose to develop stapled peptide inhibitors to intracellularly target IN-INI1 interactions. These studies are likely to lead to the development of novel anti-viral biologics to inhibit HIV-1 particle production and/or particle morphogenesis.