Inorganic polyhedral metallacarborane inhibitors of HIV protease: a new approach to overcoming antiviral resistance

J Med Chem. 2008 Aug 14;51(15):4839-43. doi: 10.1021/jm8002334. Epub 2008 Jul 4.


HIV protease (PR) is a prime target for rational anti-HIV drug design. We have previously identified icosahedral metallacarboranes as a novel class of nonpeptidic protease inhibitors. Now we show that substituted metallacarboranes are potent and specific competitive inhibitors of drug-resistant HIV PRs prepared either by site-directed mutagenesis or cloned from HIV-positive patients. Molecular modeling explains the inhibition profile of metallacarboranes by their unconventional binding mode.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boron Compounds / chemistry*
  • Boron Compounds / pharmacology*
  • Crystallography, X-Ray
  • Drug Resistance, Viral / drug effects*
  • HIV Protease / chemistry
  • HIV Protease / genetics
  • HIV Protease / metabolism*
  • HIV Protease Inhibitors / chemistry*
  • HIV Protease Inhibitors / pharmacology*
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • Metals / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Mutation / genetics


  • Boron Compounds
  • HIV Protease Inhibitors
  • Metals
  • HIV Protease