May 142008
ResearchBlogging.orgA recent episode of South Park featured a story in which two of the main characters got infected with HIV and discovered that the cure for AIDS is an injection of about $200,000. As any viewer of the series would expect, the episode is crude and vulgar, and it wobbles to and fro over the line between humor and offensiveness. Yet the episode might also turn out to be oddly prescient, if research described in an upcoming JACS article bears further fruit. As it turns out, researchers from UNC, the University of Colorado, and NC State have had some success in inhibiting HIV activity using drug-coated nanoparticles, made out of gold.

The approach Bowman et al. use is based on the idea of multivalence, which is the operating principle of Velcro. A single hook-loop interaction between two pieces of fabric usually isn’t enough to keep them fastened together. However, by having a large number of relatively weak interactions a strong connection can be made. Many biological systems make use of the same principle, using many weak interactions between repeating units to produce high overall affinity. The researchers set out to apply this idea to medicine, using many copies of a low-affinity drug attached to a nanoparticle.

The drug the authors used is based on a compound designated TAK-779, which is effective at preventing HIV virions from fusing with T cells, but also has some unpleasant properties for patients. The authors lopped off the part of the molecule that causes these problems, but doing so also removes most of its ability to fight HIV. So, they linked this new compound (called SDC-1721) to the gold particles at a ratio of about 12 molecules SDC-1721 per particle. In cultured cells, the nanoparticle-linked drug had an IC50 similar to TAK-779, even though SDC-1721 by itself was totally ineffective at preventing infection. Cutting the number of SDC-1721 molecules per particle to ~1 removed the inhibitory effect, proving that the multivalent approach was critical.

This is of course no demonstration of in vivo effectiveness, and there’s no telling whether the nanoparticle will have side-effects that are better or worse than TAK-779. However, if this initial success is borne out by further trials this may be a promising angle on treatments. One of the advantages to this approach is that it has some ability to counter resistance built into it because of the multivalent binding. Even if a virus evolves a lower affinity for the drug, the weak binding of many ligands, and the increased effective local concentration of those ligands, may be enough to rescue inhibitory activity. Injecting yourself with money is no way to cure anything, but it is possible that in the future we will attack viruses by injecting patients with (drug-laden) gold.

1. Bowman, M., Ballard, T.E., Ackerson, C.J., Feldheim, D.L., Margolis, D.M., Melander, C. (2008). Inhibition of HIV Fusion with Multivalent Gold Nanoparticles. Journal of the American Chemical Society DOI: 10.1021/ja710321g

 Posted by at 2:29 PM

  One Response to “Gold dust vs. the virus”

  1. I hear that Thomas Eric Ballard guy who worked on this paper is a total STUD in the lab

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