Fullerene, discovered in 1985, is a family of carbon allotropes – molecules composed entirely of carbon, which form a hollow sphere, ellipsoid, tube, or plane. Spherical fullerenes are also called “buckyballs.” Fullerenes are under research in relation to binding specific antibiotics to target specific bacteria, viruses, and even cancer cells such as melanoma.
An international team including two groups in Greece, one in Germany, one in Italy, and Professor Andrew Barron’s group at Rice University took on the task of testing whether the fullerene can be used as a means of combating HIV. The researchers used computer simulations to test more than a hundred fullerenes and checked whether any of them had the ability to inhibit a strain of the HIV virus by blocking its binding pocket – the area by which the virus attaches itself to cellular proteins.
“There are a lot of people doing this kind of research, but it tends to be one group or one pharmaceutical company taking a shotgun approach – make a molecule and try it out, then make another molecule and try it out,” said Barron, Rice’s Charles W. Duncan Jr.-Welch Professor of Chemistry and Material Science. “This is interesting because we’re tackling an important problem in a very rational way.”
The use of simulation to narrow down the scope of fullerenes to the useful ones is a low cost and efficient approach to drug design. “A long time ago, people noticed that C-60 fits perfectly into the hydrophobic pocket in HIV, and it has an inhibition effect,” Barron said. “It’s not particularly strong, but there’s potentially a very strong binding effect. The problem is, it’s not the perfect unit.” The objective was to find an existing fullerene derivative molecule that could be easily modified to become the perfect unit.
“We began thinking about a very simple experiment to calculate the binding efficiency of a molecule in the HIV pocket, then calculate that for a series of molecules, decide which one is best, make that molecule in real life, and see if it correlates,” Barron said. “If it does, then you’ve got a way to design your ultimate molecule. Our work was the first step in the process.”
The computer based calculations found two good fits among the multitude of fullerene derivatives tested. The scientists are now working to enhance the binding abilities in order to create the perfect molecule. Their hope is to create a molecule that would seal the HIV binding site completely and could also be ‘fine-tuned’ for various HIV strains.
However promising their results seem to be, the researchers encourage caution. “This is just one component of the problem – we’re not going to cure HIV,” said Barron. At the moment, the team just hopes to develop a method for the rapid creation of drugs to fight different strains of HIV and other diseases.
TFOT has previously brought you an article on a potential cure for HIV accidentally discovered in Berlin. More recently, we’ve covered the research of receptors in connection to HIV, conducted by scientists from Cornell University.
For more information on the fullerene’s battle against HIV please visit the Rice University news page.
Icon image: C60 bucky ball with isosurface of ground state electron density (Credit: Wikimedia Commons user Itamblyn)