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Novel Histone Deacetylase Inhibitors and HIV-1 Latency-Reversing Agents Identified by Large-Scale Virtual Screening by Donya Naz Divsalar; Conrad Veranso Simoben; Cole Schonhofer; Khumoekae Richard; Wolfgang Sippl; Fidele Ntie-Kang; Ian Tietjen is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Novel Histone Deacetylase Inhibitors and HIV-1 Latency-Reversing Agents Identified by Large-Scale Virtual Screening about?

Current antiretroviral therapies used for HIV management do not target latent viral reservoirs in humans. The experimental “shock-and-kill” therapeutic approach involves use of latency-reversal agents (LRAs) that reactivate HIV expression in reservoir-containing cells, followed by infected cell elimination through viral or host immune cytopathic effects. Several LRAs that function as histone deacetylase (HDAC) inhibitors are reported to reverse HIV latency in cells and in clinical trials; however, none to date have consistently reduced viral reservoirs in humans, prompting a need to identify new LRAs. Toward this goal, we describe here a virtual screening (VS) approach which uses 14 reported HDAC inhibitors to probe PubChem and identifies 60 LRA candidates. We then show that four screening “hits” including (S)-__N__-Hydroxy-4-(3-methyl-2-phenylbutanamido)benzamide (compound **15**), __N__-(4-Aminophenyl)heptanamide (**16**), __N__-[4-(Heptanoylamino)phenyl]heptanamide (**17**), and 4-(1,3-Dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-__N__-(2-hydroxyethyl)butanamide (**18**) inhibit HDAC activity and/or reverse HIV latency __in vitro__. This study demonstrates and supports that VS-based

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Author

Donya Naz Divsalar; Conrad Veranso Simoben; Cole Schonhofer; Khumoekae Richard; Wolfgang Sippl; Fidele Ntie-Kang; Ian Tietjen

Published

2020

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)