Despite major advances in antiretroviral therapy, HIV remains incurable due to the persistence of latent viral reservoirs that evade immune clearance and reignite infection if treatment is stopped. Current eradication strategies, such as the widely explored “kick and kill” approach, have shown limited success because reactivated infected cells are not efficiently eliminated. There is therefore a critical unmet need for innovative therapeutic concepts that prevent viral rebound and selectively eliminate infected cells.
The Super-HIPPO project addresses this challenge by developing a fundamentally new strategy termed “lock-in and apoptosis.” Instead of reactivating latent virus, this approach blocks HIV assembly at the host cell membrane and simultaneously triggers programmed cell death in infected cells. The strategy targets the matrix (MA) domain of the HIV-1 Gag polyprotein, a key component required for viral particle formation through its interaction with host cell phosphoinositides.
Building on earlier proof-of-concept studies, the project aimed to design and optimize a novel artificial phosphoinositide derivative (Super-HIPPO) with enhanced biological activity and improved intracellular delivery. The overarching objective was to generate a new class of anti-HIV agents capable of suppressing virus production and promoting selective apoptosis of infected cells, thereby contributing to long-term HIV eradication efforts.
At a broader level, the project supports EU priorities in global health, innovation in antiviral therapies, and preparedness against persistent and emerging infectious diseases. By combining medicinal chemistry, nanotechnology, molecular Biology, and structural biology, Super-HIPPO establishes a scalable pathway toward transformative HIV therapies with potential impact well beyond the lifetime of the project.
