The monoclonal antibodies 1696 and F11.2.32 strongly inhibit the activity of wild-type HIV-1 protease (PR) by binding to epitopes at the enzyme N-terminus (residues 1-6) and flap residues 36-46, respectively. Here we demonstrate that these antibodies are also potent inhibitors of PR variants resistant to active-site inhibitors used as anti-AIDS drugs. Our in vitro experiments revealed that the inhibitory potency of single-chain fragments (scFv) of these antibodies is not significantly affected by the presence of mutations in PR; inhibition constants for drug-resistant protease variants are 5-11 nM and 13-169 nM for scFv1696 and for scFvF11.2.32, respectively. Tethered dimer of HIV-1 PR variant proved to be a model protease variant resistant to dissociative inhibition by 1696, and, strikingly, it also displayed resistance to inhibition by F11.2.32 suggesting that dimer dissociation also plays a role in the inhibitory action of F11.2.32.

• MeSH
• dimerizace MeSH
• financování organizované MeSH
• genetická variace MeSH
• HIV infekce farmakoterapie   virologie   MeSH
• HIV-1 enzymologie   genetika   účinky léků   MeSH
• HIV-proteasa genetika   imunologie   účinky léků   MeSH
• imunoglobuliny - fragmenty farmakologie   imunologie   MeSH
• inhibitory HIV-proteasy farmakologie   MeSH
• lidé MeSH
• molekulární modely MeSH
• monoklonální protilátky farmakologie   imunologie   MeSH
• mutace MeSH
• rekombinantní proteiny farmakologie   imunologie   MeSH
• virová léková rezistence genetika   MeSH
• vysoce aktivní antiretrovirová terapie MeSH
• Check Tag
• lidé MeSH