August 6, 2019
University of Texas at Galveston
Credit: UTMB
Researchers at the University of Texas Medical Branch in Galveston have discovered a potential new drug that works with a person's own HIV-infected body to further suppress the ever-present but silent virus that available HIV treatments cannot combat.
While the potential new drug could complement current antiretroviral therapy (ART) medications for HIV, it may also lead to HIV remission without lifelong medication. The findings are published in the Journal of Clinical Investigation.
The HIV virus integrates into the genetic code of the infected person and establishes a constant latent infection, creating a major treatment challenge. Because of this, current antiretroviral medications fail to cure the virus, and when someone stops taking the medication, the virus almost always begins to multiply and wreak havoc. Drug resistance is also a public health problem with ART medications. Being able to induce sustained HIV remission without ART is a major goal for HIV treatment.
“We are the first to demonstrate that the human BRD4 protein and its associated machinery can be harnessed to suppress latent HIV,” said senior author Haitao Hu, assistant professor at UTMB in the Department of Microbiology and Immunology. “Our findings are exciting because they not only enhance our understanding of the biology of epigenetic regulation of HIV, but also present a promising approach for developing probes and/or therapeutic agents for HIV silencing, with the hope that this will eventually lead to a cure for the virus.”
In the laboratory study, researchers found that the BRD4 protein plays a key role in regulating the production of new copies of the HIV gene. The team successfully designed, synthesized, and screened a series of small molecules to selectively program BRD4 to suppress HIV and identified a lead compound called ZL0580. They tested the lead molecule in HIV infection models and found that it significantly delayed the reactivation of latent HIV after cessation of ART in the blood cells of HIV-infected individuals treated with ART.
“We will continue to optimize the chemical structure and effectiveness of this class of molecules and conduct safety testing in cell and animal studies,” said co-senior author Jia Zhou, a professor at UTMB in the Department of Pharmacology and Toxicology. “We look forward to the time when we can begin clinical trials so that this approach can start helping people infected with HIV.”
Further information: Qingli Niu et al. Structure-guided drug design identifies a BRD4-selective small molecule that suppresses HIV, Journal of Clinical Investigation (2019). DOI: 10.1172/JCI120633
Journal information: Journal of Clinical Investigation. Provided by the Medical Branch of the University of Texas at Galveston.
From: https://medicalxpress.com/news/2019-08-newly-approach-silencing-hiv-infection.html