New Approach Developing To Shows Promise In Silencing HIV Infection

The study developing an new approach for showing  promise in silencing HIV infection; by discovering a new potential medication; that works with an HIV-infected person’s own body to further suppress the ever present but silent virus that available HIV treatments are unable to combat. Although the potential new drug could complement the current HIV anti-retroviral therapy (ART) medications, it may also be possible that it could lead to HIV remission without a lifetime of taking ART medications.

HIV integrating its provirus into the host genome and establishes latent infection. Antiretroviral therapy (ART) can control HIV viremia, but cannot eradicate or cure the virus. Approaches targeting host epigenetic machinery to repress HIV, leading to an aviremic state free of ART, are needed. Bromodomain and extraterminal (BET) family protein BRD4 is an epigenetic reader involved in HIV transcriptional regulation.

Silencing HIV infection

Using structure-guided drug design, we identified a small molecule (ZL0580) that induced epigenetic suppression of HIV via BRD4. The HIV virus gets integrating into the infecting person’s genetic coding and establishing a constant dormant infection, creating a big treatment challenge. Because of this, current ART medications fail to cure the virus and when someone stops the drug, the virus almost always begins to multiply and wreak havoc.

Drug resistance is also a public health issue with the ART medications. Being able to induce a sustained HIV remission free of ART is an important goal for HIV treatment. human BRD4 protein and its associated machinery can be harnessed to suppress dormant HIV, said senior author Haitao Hu, UTMB assistant professor in the department of microbiology and immunology.

The drug resistance

Our findings are exciting because they not only improve our understanding of the biology of HIV epigenetic regulation; they also present a promising approach for the development of probes and/or therapeutic agents for HIV silencing, hopefully leading to cure of the virus eventually. But the study finding; that the protein BRD4 plays an important role in regulating the production of new copies of the HIV gene.

The team successfully designing, synthesizing and evaluating a series of small molecules; to selectively program BRD4 to suppress HIV and identified a lead compound called ZL0580. They testing the lead molecule in HIV infection models; and finding that it significantly delayed dormant HIV reactivation; after ART cessation in blood cells of ART-treated, HIV infected people. But to optimize the chemical structure; and effectiveness of this class of molecules and conduct safety testing in cellular and animal studies.