Floudas Team Discovers HIV Inhibitors Computationally

Feb. 8, 2011

A research team led by Christodoulos Floudas, Stephen C. Macaleer '63 Professor in Engineering and Applied Science, has developed a new computational design framework for peptides that act as HIV-1 entry inhibitors. By combining sequence selection and binding affinity calculations for a range of 12-amino-acid-long peptides, the team identified the candidates which offered the “best fit” into a particular binding site on the HIV-1 virus. Five of these candidate peptides were then synthesized and tested for inhibition of HIV-1 in cell culture by team members at Johns Hopkins University. Four of the five peptides showed significant inhibition, despite being much shorter than the 36-amino-acid-long enfuvirtide, an FDA-approved HIV fusion inhibitor in use since 2003. One of the designed peptides was particularly potent, showing inhibition against even enfuvirtide-resistant strains of HIV. This work demonstrates the possibility of computationally discovering short peptides that can effectively inhibit HIV-1 which avoid the limitations that can sometimes plague longer peptides, such as poor bioavailability, high production cost, and short half-life. For more information, see the news story posted on the Princeton University homepage, or for those with library access, the Biophysical Journal research article, “Discovery of Entry Inhibitors for HIV-1 via a New De Novo Protein Design”.