High-Affinity Recognition of HIV-1 Frameshift-Stimulating RNA Alters Frameshifting in Vitro and Interferes with HIV-1 Infectivity | Zendy

Leslie O. Ofori | Zendy; Thomas A. Hilimire | Zendy; Ryan P. Bennett | Zendy; Nathaniel W. Brown | Zendy; Harold C. Smith | Zendy; Benjamin L. Miller | Zendy

Open Access

High-Affinity Recognition of HIV-1 Frameshift-Stimulating RNA Alters Frameshifting in Vitro and Interferes with HIV-1 Infectivity

Author(s) -

Leslie O. Ofori,

Thomas A. Hilimire,

Ryan P. Bennett,

Nathaniel W. Brown,

Harold C. Smith,

Benjamin L. Miller

Publication year - 2014

Publication title -

journal of medicinal chemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.01

H-Index - 261

eISSN - 1520-4804

pISSN - 0022-2623

DOI - 10.1021/jm401438g

Subject(s) - translational frameshift , infectivity , frameshift mutation , chemistry , rna , stem loop , virology , translation (biology) , virus , in vitro , viral replication , luciferase , microbiology and biotechnology , ribosome , biology , messenger rna , biochemistry , transfection , mutation , gene

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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research