Targeting Tat-TAR RNA Interaction for HIV-1 Inhibition.

ABSTRACT: The HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus, Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of acetylpromazine bound to the bulge of TAR RNA, to dock compounds from the Enamine database containing over two million individual compounds. The docking procedure identified 173 compounds that were further analyzed for the inhibition of HIV-1 infection. The top ten inhibitory compounds with IC₅₀ ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC₅₀ = 2.97 μM), T0516-4834 (IC₅₀ = 0.2 μM) and T5628834 (IC₅₀ = 3.46 μM), were

SUBMITTER: Alanazi A 

PROVIDER: S-EPMC8536978 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature