Potent inhibition of drug-resistant HIV protease variants by monoclonal antibodies.


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.

DOI: 10.1016/j.antiviral.2008.01.009

Cite this paper

@article{Bartonov2008PotentIO, title={Potent inhibition of drug-resistant HIV protease variants by monoclonal antibodies.}, author={Vanda Bartonov{\'a} and Vlastimil Kr{\'a}l and Irena Sieglov{\'a} and J{\'i}r{\'i} Brynda and Milan F{\'a}bry and Magdal{\'e}na Horejs{\'i} and Milan Ko{\vz}{\'i}{\vs}ek and Kl{\'a}ra Grantz {\vS}a{\vs}kov{\'a} and Jan Konvalinka and Juraj Sedl{\'a}{\vc}ek and Pavl{\'i}na Řez{\'a}{\vc}ov{\'a}}, journal={Antiviral research}, year={2008}, volume={78 3}, pages={275-7} }