Researchers at the University of Wisconsin-Madison, working in conjunction with researchers at Weill Medical College of Cornell University, recently engineered synthetic proteins that prevent the infection of human cells by HIV. The results of their study are published online in the Proceedings of the National Academy of Sciences.

Viruses, such as HIV, usually require communication between the proteins of the virus and the proteins of the host cells in order to successfully establish the infection. The research team, led by Dr. Samuel Gellman, created molecules similar to the HIV proteins (known as gp41) that interact with human proteins during infection. These peptides (very small proteins) prevented HIV from infecting healthy host cells.

“I am excited about our results because they seem to suggest a general strategy for blocking protein-protein interactions that are important in human disease,” said Dr. Gellman.

The synthetic peptide molecules, called “foldamers,” were made from natural amino acids (the building blocks of proteins) as well as unnatural amino acids. The use of unnatural amino acids prevents the body from degrading the peptide as rapidly. This means that the drug remains effective for longer periods of time, and thus requires a lower dose.

Past attempts at creating protein mimics to block HIV infection have mostly been unsuccessful. For instance, most of the past drugs used small molecules.  However, protein-protein interactions involve large surfaces of proteins that are difficult to disrupt with small molecules.

Peptides are often very effective at interrupting protein interactions, but peptides are easily degraded by enzymes in the body and thus require high doses in humans.

The use of foldamers, therefore, solves both of these problems because they are large structures that are more stable against degradation by enzymes.

So far, foldamers have been successful in preventing HIV infection of host cells in lab tests. According to Dr. Gellman, “A great deal of development would be required before a compound of our type could be tested in humans.” Thus, there is no certainty as to whether this technology will be used in future anti-HIV drugs.

For further information, please see the study in the  Proceedings of the National Academy of Sciences (abstract).