Researchers detail HIV-1 Structure, Paving Way for Novel Antiviral Therapies
Valencia, Spain – Scientists at the Catholic University of Valencia (UCV)’s Structural and Computational Biochemistry Laboratory have published groundbreaking research in the Journal of Molecular Biology detailing the three-dimensional structure and recognition mechanism of the Rev Response Element (RRE) of HIV-1, a critical component in the virus’s replication process. The findings offer a potential new target for antiviral drug progress.
HIV-1, the virus causing AIDS, remains a leading cause of mortality globally, despite advancements in treatment. Current therapies are not curative, and an effective vaccine remains elusive. The UCV team, led by researcher José Gallego, focused on the RRE, a complex RNA structure essential for transporting viral genetic material from the cell nucleus to the cytoplasm.
“The RRE or its complex with Rev are not being addressed by any of the currently marketed antiretroviral agents,” explained Gallego.
The research, conducted by UCV researchers Matthew P. Shoemaker, saurabh Loharch, Sergio López-Núñez, and Gallego, utilized mutagenesis, fluorescence, and molecular modeling to map the RRE’s structure and its interaction with the Rev protein. This detailed understanding “opens the door to the design of new inhibitors capable of interfering with said union, thus blocking a critical step in the replication of the pathogen,” Gallego stated.
Future research will focus on the conformational dynamics of the RRE using single-molecule FRET experiments, alongside investigations into allosteric inhibitors identified through chemical fingerprinting and molecular modeling. The team also plans to optimize promising compounds through chemical synthesis and cellular studies.
“with this multidisciplinary strategy we hope to shed light on the functional dynamics of the RRE and identify leading compounds with an innovative mechanism of action, which could contribute to opening new avenues towards the cure of AIDS,” Gallego concluded.
