​Scientists have been hard at work for decades to find solutions to prevent or cure AIDS. While tritherapy significantly reduces the viral load, other therapeutic approaches are being developed. For example, for the past few years, a team from the Institute of Structural Biology has been focusing its efforts on a protein named gp120, which is found on the surface of the virus. Thanks to efforts observing and characterizing this protein, the researchers have developed a molecule targeting gp120 and which, formulated in a gel, has a microbicidal activity and is capable of preventing the infection of cells.

HIV targets white blood cells in the immune system, including certain T cells and macrophages, through the gp120 protein. "Our approach is twofold", said Hugues Lortat-Jacob, researcher at IBS. "First, we have developed mimics of the anchor point of gp120 on the immune cells. This anchoring point is the CD4 receptor, which gp120 recognizes and binds to." The mCD4 ("m" for "mimic") bind to gp120, thus trapping the virus. "We also prevent the virus from entering the cell", Lortat-Jacob said. In fact, when the viruses are capable of binding to CD4 via the gp120 protein, the latter changes conformation, thereby exposing a new region of the viral envelope involved in the recognition of the CCR5 and CXCR4 coreceptors and in the entry of the virus in the cell. "We also block this new region with a sulfopeptide called PS1, which mimicks CCR5 and CXCR4", Lortat-Jacob further explained.

The researchers then synthesized a new molecule composed of mCD4 and PS1. The new anti-HIV strategy was integrated into a microbicide gel and tested in vitro and then in vivo in a non-human primate model, in collaboration with a team from CEA-IMETI. "83% of the animals were protected from infection thanks to this gel containing this first-generation molecule", he said. The biologists and chemists are currently working to enhance the effectiveness of this molecule. They are now working on the third generation of mCD4-PS1, with activity 100 times more significant compared to the first generation.

This preventive strategy may prove to be useful in treating HIV infection.

"In fact, when our mCD4-PS1 molecules bind to gp120, the antibodies produced by the immune system could recognize the virus more easily", Lortat-Jacob said.