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Updated: May 4, 2026

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy
Published on: September 5, 2016
High-affinity recognition of HIV-1 frameshift-stimulating RNA alters frameshifting in vitro and interferes with HIV-1
Leslie O Ofori1, Thomas A Hilimire, Ryan P Bennett
1Departments of Chemistry, ‡Biochemistry and Biophysics, and §Dermatology, University of Rochester , Rochester, New York 14642, United States.
Abstract:
The life cycle of the human immunodeficiency virus type 1 (HIV-1) has an absolute requirement for ribosomal frameshifting during protein translation in order to produce the polyprotein precursor of the viral enzymes. While an RNA stem-loop structure (the "HIV-1 Frameshift Stimulating Signal", or HIV-1 FSS) controls the frameshift efficiency and has been hypothesized as an attractive therapeutic target, developing compounds that selectively bind this RNA and interfere with HIV-1 replication has proven challenging. Building on our prior discovery of a "hit" molecule able to bind this stem-loop, we now report the development of compounds displaying high affinity for the HIV-1 FSS. These compounds are able to enhance frameshifting more than 50% in a dual-luciferase assay in human embryonic kidney cells, and they strongly inhibit the infectivity of pseudotyped HIV-1 virions.
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