nsc-260594 and HIV-Infections

RNA-protein interactions are vital throughout the HIV-1 life cycle for the successful production of infectious virus particles. One such essential RNA-protein interaction occurs between the full-length genomic viral RNA and the major structural protein of the virus. The initial interaction is between the Gag polyprotein and the viral RNA packaging signal (psi or Ψ), a highly conserved RNA structural element within the 5'-UTR of the HIV-1 genome, which has gained attention as a potential therapeutic target. Here, we report the application of a target-based assay to identify small molecules, which modulate the interaction between Gag and Ψ. We then demonstrate that one such molecule exhibits potent inhibitory activity in a viral replication assay. The mode of binding of the lead molecules to the RNA target was characterized by ¹H NMR spectroscopy.

Topics: Anti-HIV Agents; Binding Sites; Cell Survival; Drug Evaluation, Preclinical; gag Gene Products, Human Immunodeficiency Virus; HEK293 Cells; HeLa Cells; HIV Infections; HIV-1; Humans; Models, Molecular; Molecular Targeted Therapy; Nucleic Acid Conformation; Nucleic Acid Denaturation; Osmolar Concentration; Quinolinium Compounds; Ribonucleoproteins; RNA, Spliced Leader; RNA, Viral; Schiff Bases; Small Molecule Libraries; Virus Replication