BREAKING! HIV News: Scientists Discover That The Phytochemical Hopeaphenol Inhibits Reactivation Of HIV Viral Reservoirs!

The Phytochemical Hopeaphenol , A Natural Stilbenoid, Inhibits HIV Transcription by Targeting Both PKC and NF-κB Signaling and Cyclin-Dependent Kinase 9


 
HIV News: A new breakthrough discovery in HIV research hold promise in enhancing the efficacy of current HIV treatments and improve the quality for individuals living with HIV.
 
Researchers from the Wistar Institute, Philadelphia, Pennsylvania-USA have in a new study discovered that the phytochemical Hopeaphenol inhibits reactivation of HIV viral reservoirs!
 
Hopeaphenol is a naturally occurring plant polyphenol It is composed of resveratrol units and is a resveratrol tetramer. It has been found in the plants that belong to the family Dipterocarpaceae like Shorea ovalis and other plant sources.
 
Interestingly, the same research team from Wistar Institute in a previous research found that hopeaphenol and related stilbenoid analogues may act as inhibitors of viral entry across multiple SARS-CoV-2 variants!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597786/
 
The study team also comprised of scientists from Simon Fraser University, Burnaby, British Columbia-Canada and Griffith University, Brisbane-Australia and Jonathan Lax Immune Disorders Treatment Center, Philadelphia-USA.
 
Despite the effectiveness of combination antiretroviral therapy (cART), individuals living with HIV (PLWH) still retain replication-competent and transcriptionally active virus within their infected cells. This persistence can result in ongoing viral antigen production, chronic inflammation, and an elevated risk of age-related comorbidities.
 
In order to discover new agents capable of inhibiting postintegration HIV beyond the scope of cART, the study team conducted a screening process with a library of 512 pure compounds derived from natural products.
 
The study team They identified (–)-hopeaphenol as a compound capable of inhibiting HIV postintegration transcription at low to submicromolar concentrations without causing cytotoxicity.
 
The study team employed a combination of global RNA sequencing, plasmid-based reporter assays, and enzyme activity studies to reveal that hopeaphenol can effectively inhibit protein kinase C (PKC)- and downstream NF-κB-dependent HIV transcription. Moreover, it can suppress a subset of PKC-dependent T-cell activation markers, including interleukin-2 (IL-2) cytokine production and the RNA production of CD25 and HLA-DRB1. However, hopeaphenol does not substantially inhibit early PKC-mediated T-cell activation marker CD69 production, IL-6 production, or NF-κB signaling triggered by tumor necrosis factor alpha (TNF-α).
 
Additionally, the study findings demonstrated that hopeaphenol has the ability to inhibit the enzymatic activity of cyclin-dependent kinase 9 (CDK9), which is required for HIV transcription. The compound was also found to inhibit HIV replication in peripheral blood mononuclear cells (PBMCs) infected in vitro and to suppress viral reactivation in CD4+ cells derived from PLWH.
 
In conclusion, the study findings identify hopeaphenol as a novel inhibitor that targets a specific subset of PKC-mediated T-cell activation pathways, in addition to CDK9, in order to impede HIV expression. Therapies based on hopeaphenol could potentially complement current antiretroviral treatments, which do not target cell-associated HIV RNA and residual antigen production in PLWH. As a result, hopeaphenol-based therapies may hold promise in enhancing the efficacy of existing HIV treatments, ultimately benefiting those living with the virus by reducing the long-term complications associated with HIV infection and improving overall health and well-being.
 
The study findings were published in the peer reviewed journal: Antimicrobial Agents and Chemotherapy (ASM Journals).
https://journals.asm.org/doi/10.1128/aac.01600-22
 
According to HIV News updates, as of the year 2022, an estimated 1.2 million individuals in the United States are grappling with the human immunodeficiency virus (HIV). Although antiretroviral therapies have empowered numerous people to lead productive and symptom-free lives, a cure that permanently eradicates HIV from an infected person's system remains elusive.
 
Nevertheless, scientists at The Wistar Institute, a globally renowned biomedical research center specializing in cancer, immunology, infectious diseases, and vaccine development, have honed in on a compound that shows promise in targeting HIV reservoirs. These reservoirs persist in individuals living with HIV despite the administration of anti-HIV treatments.
 
The study team highlighted hopeaphenol, a naturally occurring plant-based compound, as possessing antiviral properties effective against HIV. The compound not only obstructs viral replication but also inhibits the reactivation of the latent "viral reservoir" that lingers within human immune cells even after anti-HIV therapy. This reservoir can generate new viruses at any time, regardless of whether patients are undergoing antiretroviral therapy (ART) and showing no viral symptoms.
 
Dr Ian Tietjen, Ph.D., the paper's lead author and a research assistant professor in Luis Montaner's laboratory at Wistar's Vaccine & Immunotherapy Center, emphasized the significance of this discovery.
 
According to Dr Tietjen, although anti-HIV therapy can suppress symptoms, it fails to eliminate the underlying HIV reservoir's potential to resurface. The virus continues to exist and remains somewhat active, causing the immune system to be constantly stressed.
 
Dr Tietjen further explained that the persistent expression of HIV can stress immune cells even in the presence of anti-HIV therapy. This has been associated with inflammation and an elevated risk of cancers, metabolic diseases, heart diseases, and other conditions linked to advanced aging in individuals living with HIV. Therefore, a compound like hopeaphenol could potentially prevent the HIV reservoir from reactivating, reducing the immune system's stress and potentially decreasing the occurrence of age-related conditions.
 
Dr Tietjen and his team first identified hopeaphenol's potential for suppressing HIV expression by testing a set of 512 compounds. Hopeaphenol emerged as the most active, prompting further testing. Collaborating with students from Cheyney University and Philadelphia high school students participating in Wistar's Education and Training Programs, the team verified their findings and analyzed the compound's mechanism of action.
 
Subsequently, they conducted two experiments to demonstrate hopeaphenol's therapeutic potential against HIV.
 
In the first experiment, the researchers isolated lymphocytes (a type of white blood cell) from human blood samples and infected these cells with HIV in a laboratory setting. After allowing the virus to replicate, they treated the infected cells with hopeaphenol, which halted the virus's replication. In the second experiment, the team took CD4+ T cells, also known as "helper T-cells," from several HIV-positive individuals receiving anti-HIV therapy. They divided the cells into two groups: one pre-treated with hopeaphenol and the other (the control group) left untreated.
 
The scientists then triggered the cells with viral reservoirs to start producing the virus. They observed that cells pre-treated with hopeaphenol exhibited reduced viral production, indicating hopeaphenol's ability to dampen viral reactivation.
 
Dr Tietjen noted that these observations suggest hopeaphenol might help silence the HIV reservoir by inhibiting viral reactivation, something not achieved by current anti-HIV medications.
 
Previous research has shown that hopeaphenol is well tolerated in animal models, and since it can be derived from various plant sources, its isolation can be easily scaled up.
 
Considering these factors and the results of his study, Dr Tietjen is optimistic that hopeaphenol may eventually contribute to an improved quality of life for individuals living with HIV. However, further research is necessary before the compound can be tested on human subjects.
 
Dr Tietjen said, "I think in time it could become a promising additive on top of existing antiretrovirals as a more potent anti-HIV therapy." This breakthrough could potentially pave the way for a more effective treatment that goes beyond the scope of current antiretroviral therapies, providing an additional layer of protection against the virus.
 
The development of hopeaphenol as an effective treatment against HIV will require a series of rigorous clinical trials to assess its safety and efficacy in human subjects. This will likely include evaluating the compound's pharmacokinetics and pharmacodynamics, determining the optimal dosing regimen, and understanding any potential side effects or interactions with other medications.
 
If hopeaphenol proves successful in clinical trials, it could become a vital component in the arsenal of HIV treatments, offering a more comprehensive approach to managing the virus in affected individuals. This novel treatment could also help to lessen the burden on healthcare systems by reducing the long-term complications associated with HIV infection and improving the overall health and wellbeing of those living with the virus.
 
In summary, the discovery of hopeaphenol's antiviral properties offers a promising avenue for future HIV treatment development. The compound's ability to target and suppress HIV reservoirs while inhibiting viral reactivation could potentially revolutionize the way HIV is managed and treated, bringing hope to millions of people worldwide who are affected by this life-altering virus. While further research is necessary, hopeaphenol represents a significant step forward in the ongoing battle against HIV and the quest to find a cure.
 
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