New `drug` blocks replication of AIDS virus for first time
Washington: In a first, Spanish scientists have designed small synthetic molecules that can block the replication of the deadly AIDS virus.
The newly designed molecules inhibit the output of genetic material of the virus from the infected cell nucleus to the cytoplasm, thus the virus replication is blocked and avoids the infection of other cells.
This achievement has been obtained for the "first time in the world" by a group of researcher led by Jose Gallego from Universidad Catolica de Valencia.
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 to reproduce the interactions of one of the proteins encoded by the virus, the viral protein 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.
Scientists verified experimentally that the terphenyls were capable of joining the Rev receptor in the viral RNA and inhibit the interaction between this RNA and the protein.
The molecules were synthesised in professor Santos Fustero's organic Chemistry laboratory in the Principe Felipe Research Centre and the University of Valencia.
The group of Jose Alcami in the Instituto de Salud Carlos III demonstrated that the inhibitors block the replication of the HIV-1 and inhibit the function of the Rev protein, confirming this way the validity of the models generated by computer.
Pharmaceutical companies have focused on the development of medicines that act on target proteins, as the approach to the receptors made out of RNA is considerably complex.
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, researchers said.
The study was published in the journal Angewandte Chemie International Edition.
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