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

Antimicrob Agents Chemother

In this study, researchers investigated a natural compound called (-)-Hopeaphenol to understand its potential in combating HIV infection. HIV is a virus that attacks the immune system, leading to AIDS if left untreated. Current treatments for HIV focus on controlling the virus, but they often come with side effects that can reduce health over the long-term. The researchers found that (-)-Hopeaphenol can hinder the transcription process of HIV, which is essential for the virus to replicate and spread within the body. By targeting the transcription process, (-)-Hopeaphenol aims to reduce the production of new virus particles, slowing down the progression of the infection.

The compound achieves its effects through inhibiting both protein kinase C (PKC) and Nuclear Factor kappa B (NF-κB), which are signaling proteins that cause HIV transcription and production of new virus from latent HIV reservoirs. Additionally, the researchers found that (-)-Hopeaphenol impacts a protein called Cyclin-Dependent Kinase 9 (CDK9), which acts separately from PKC and NF-κB but is also required for HIV transcription. Finally, the researchers showed that by targeting these two cell pathways, (-)-Hopeaphenol can dampen the ability of the virus to re-awaken, start transcription, and make new virus particles in subsequent stimulations.

The discovery of (-)-Hopeaphenol’s ability to target multiple pathways involved in HIV replication is particularly promising. Combining these effects could lead to more effective treatments and potentially slow down the development of drug resistance, a common challenge in HIV therapy. However, it is essential to highlight that this research is still in the early stages, and further studies are needed to fully understand the compound’s potential and its safety for human use. However, these findings open new avenues for developing novel and potentially more effective therapies against HIV that may improve current antiretroviral therapies and reduce current side effects.

SANTHE is an Africa Health Research Institute (AHRI) flagship programme funded by the Science for Africa Foundation through the DELTAS Africa programme; the Bill & Melinda Gates Foundation; Gilead Sciences Inc.; and the Ragon Institute of Mass General, MIT, and Harvard.