Identification of benzazole compounds that induce HIV-1 transcription

• Published in: PloS one Vol. 12; no. 6; p. e0179100
• Main Authors: Graci, Jason D, Michaels, Daniel, Chen, Guangming, Schiralli Lester, Gillian M, Nodder, Sarah, Weetall, Marla, Karp, Gary M, Gu, Zhengxian, Colacino, Joseph M, Henderson, Andrew J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-06-2017; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Azoles - chemistry; Azoles - pharmacology; Benzene - chemistry; Benzene - pharmacology; Biology and Life Sciences; Cell activation; Cell Line; Dentistry; Dosage and administration; Drug therapy; Epigenetics; Gene expression; Histone deacetylase; HIV; HIV infections; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus; Humans; In vitro methods and tests; Infections; Infectious diseases; Inhibition; Kinases; Latency; Lymphocytes; Lymphocytes T; Medicine; Medicine and Health Sciences; Patients; Public health; Structure-activity relationships; Therapy; Transcription; Transcription (Genetics); Transcription, Genetic - drug effects; Viruses; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0179100

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.