In a report published today in Nature Chemical Biology, researchers demonstrated a new molecule that prevents HIV from infecting white blood cells by blocking binding to the cells’ surface.

For HIV to infect a cell, the virus must first bind to proteins on the cell’s surface. The process is almost like fitting puzzle pieces: HIV has a protein on its surface, gp120, that fits onto a protein called CD4 located on the surface of white blood cells.  Once the virus protein attaches to the white blood cell protein, the virus can merge with the cell and infect it.

Because of this binding procedure, immune cells with CD4 on their surface are the primary targets for HIV infection. Counting the number of CD4-positive immune cells in the bloodstream (a CD4 count) is typically used to determine how advanced an HIV infection is. Low CD4 counts, found in individuals where the virus has killed most of the CD4-positive white blood cells, indicate an advanced stage of AIDS.

In this study, scientists created a new puzzle piece: a compound that binds and covers the important parts of the HIV protein gp120. This prevents HIV from binding to CD4 and also to a second cell surface component called heparan sulfate. The scientists found that molecules that only block CD4 binding, or only block heparan sulfate binding, were not as effective as the combination molecule that blocks both.

“This new strategy results in very effective inhibition of HIV infection, at least in cellular assays,” said Professor Hugues Lortat-Jacob, a scientist at the Centre National de la Recherche Scientifique in France and an author of the study. “This molecule, acting very early in the viral life cycle, has potential for both prevention and therapy following topical and/or parenteral (intravenous) application.”

Since the new compound prevents HIV from infecting white blood cells, it would be classified as an entry inhibitor, a relatively new type of AIDS drug. One advantage of entry inhibitors is that since they are newer and work differently than most other HIV drugs, they are often effective even against drug-resistant HIV.

This new report is preliminary, and “there is still much work to do” before the new compound would be ready for clinical trials, said Prof. Lortat-Jacob. “Our molecule is difficult to synthesize, and although its preparation can be scalable at the industrial level, its cost might be important.” His research team is currently in the process of simplifying the molecule’s structure for use in animal studies.

For more information, please see the article in Nature Chemical Biology (abstract).