Potent inhibition of drug-resistant HIV protease variants by monoclonal antibodies.
Antiviral Res
; 78(3): 275-7, 2008 Jun.
Article
en En
| MEDLINE
| ID: mdl-18329737
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Variación Genética
/
Proteínas Recombinantes
/
Fragmentos de Inmunoglobulinas
/
Proteasa del VIH
/
VIH-1
/
Farmacorresistencia Viral
/
Anticuerpos Monoclonales
Límite:
Humans
Idioma:
En
Revista:
Antiviral Res
Año:
2008
Tipo del documento:
Article
País de afiliación:
República Checa