Spanish researchers design molecule that stops AIDS virus replicating

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 its replication.

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: 10.1002/anie.201309856


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