Spanish researchers design molecule that stops AIDS virus
23 December 2013
A multidisciplinary team of scientists from Spanish universities
and research centres has designed small synthetic molecules capable
of attaching to the genetic material of the AIDS virus and blocking
The molecules inhibit the output of genetic material of the virus
from the infected cell nucleus to the cytoplasm, stopping
replication and infection of other cells.
The genetic material of the AIDS virus, or HIV-1, is formed by
ribonucleic acid (RNA), and encodes several proteins that allow it
to penetrate the human cells and reproduce within them. The new
virus inhibitors, called terphenyls, were designed by computer at
the Universitat Católica de Valencia to reproduce the interactions
of one of the proteins encoded by the virus, called Rev.
The terphenyls join Rev’s receptor in the viral RNA, preventing
the interaction between the protein and its RNA receptor. This
interaction is necessary for the virus genetic material to leave the
infected cell nucleus and, thus, it is essential for the survival of
HIV-1. The fact that the terphenyls block the virus genetic material
output of the cell prevents the infection of other cells.
The molecules were synthesised in the Príncipe Felipe Research
Centre and the University of Valencia, while the Instituto de Salud
Carlos III conducted the experiments that demonstrated that the
inhibitors block the replication of the HIV-1 and inhibit the
function of the Rev protein.
Although several natural antibiotics act at the bacterial
ribosomal RNA level, up to now designing by computer a new synthetic
chemical entity capable of joining RNA target and have a relevant
pharmacological effect was not possible. The terphenyl structures
identified in this research could open new ways to approach other
therapeutic targets formed by nucleic acids.
The results of this research have been the objectives of a patent
application, and the three laboratories involved in the research
keep their collaboration with the objective of improving the
pharmacological properties of new Rev inhibitors.
González-Bulnes, L., Ibáñez, I., Bedoya, L. M., Beltrán, M.,
Catalán, S., Alcamí, J., Fustero, S. and Gallego, J. (2013),
Structure-Based Design of an RNA-Binding p-Terphenylene Scaffold
that Inhibits HIV-1 Rev Protein Function. Angew. Chem. Int. Ed.. doi: