Open AccessIdentification of benzazole compounds that induce HIV-1 transcription
Author(s) -
Jason D. Graci,
Daniel Michaels,
Guangming Chen,
Gillian M. Schiralli Lester,
Sarah B. Nodder,
Marla Weetall,
Gary M. Karp,
Zhengxian Gu,
Joseph M. Colacino,
Andrew J. Henderson
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0179100
Subject(s) - provirus , antiretroviral therapy , medicine , human immunodeficiency virus (hiv) , immunology , histone deacetylase , bioinformatics , biology , computational biology , histone , viral load , genetics , genome , gene
Despite advances in antiretroviral therapy, HIV-1 infection remains incurable in patients and continues to present a significant public health burden worldwide. While a number of factors contribute to persistent HIV-1 infection in patients, the presence of a stable, long-lived reservoir of latent provirus represents a significant hurdle in realizing an effective cure. One potential strategy to eliminate HIV-1 reservoirs in patients is reactivation of latent provirus with latency reversing agents in combination with antiretroviral therapy, a strategy termed “shock and kill”. This strategy has shown limited clinical effectiveness thus far, potentially due to limitations of the few therapeutics currently available. We have identified a novel class of benzazole compounds effective at inducing HIV-1 expression in several cellular models. These compounds do not act via histone deacetylase inhibition or T cell activation, and show specificity in activating HIV-1 in vitro. Initial exploration of structure-activity relationships and pharmaceutical properties indicates that these compounds represent a potential scaffold for development of more potent HIV-1 latency reversing agents.