Compounds that block latent HIV-1 reactivation were found

In a new study, researchers from the University of Pittsburgh in the United States identified compounds that block latent HIV-1 reactivation in human cell systems containing latent HIV-1. The findings were published In the December 3, 2018 issue of the journal Antimical Agents and Infanty under the title "Editors of Signaling Pathways That Block Reversal of HIV-1 Latency."
the compounds tested by the researchers came from a chemical library of 418 "kinase inhibitors." Kinase targets a range of signaling paths within cells and regulates vital cellular functions such as DNA transcription, protein translation, and cell metabolism. These signaling paths include signaling paths that reverse the latent nature of HIV-1 viruses that have been integrated into the human genome. As a result, the study could lead to the development of a permanent way to suppress HIV infection, said lead author Benni E. Vargas, a doctoral student in the Department of Microbiology and Immunology at the University of Pittsburgh School of Medicine.
the researchers used HIV-1 to infect 24ST1NLESG cell line and let them lurk in those cells. The viruses carry a "report gene" that glows when they are reactivated, so they know if that reactivation will occur. They then added a small molecule compound that activates HIV-1 to these in-body cultured cell lineages and exposed each cell culture to one of the 418 different kinase inhibitors.
potential for these kinase inhibitors is that they may be toxic to human cells. The researchers measured this toxicity by measuring ATP produced in the mitochondrials of cells. Vargas said a significant decrease in the number of ATPs compared to normal indicates the toxicity of kinase inhibitors. Regardless of the presence of latent reversal reagents, they found 12 kinase inhibitors blocking latent HIV-1 reactivation. Of these 12 kinase inhibitors, Daruschet (an aurora kinase inhibitor) and PF-3758309 (a PAK4 inhibitor) are the most powerful and least toxic. These latent HIV-1 reactivation inhibitors are expected to be used in combined with antiretroviral drugs to reduce residual HIV-1 viral load in the blood. (Bio Valley)