Antiviral breadth and combination potential of peptide triazole HIV-1 entry inhibitors.
Antimicrob Agents Chemother
; 56(2): 1073-80, 2012 Feb.
Article
em En
| MEDLINE
| ID: mdl-22083481
ABSTRACT
The first stage of human immunodeficiency virus type 1 (HIV-1) infection involves the fusion of viral and host cellular membranes mediated by viral envelope glycoprotein gp120. Inhibitors that specifically target gp120 are gaining increased attention as therapeutics or preventatives to prevent the spread of HIV-1. One promising new group of inhibitors is the peptide triazoles, which bind to gp120 and simultaneously block its interaction with both CD4 and the coreceptor. In this study, we assessed the most potent peptide triazole, HNG-156, for inhibitory breadth, cytotoxicity, and efficacy, both alone and in combination with other antiviral compounds, against HIV-1. HNG-156 inhibited a panel of 16 subtype B and C isolates of HIV-1 in a single-round infection assay. Inhibition of cell infection by replication-competent clinical isolates of HIV-1 was also observed with HNG-156. We found that HNG-156 had a greater than predicted effect when combined with several other entry inhibitors or the reverse transcriptase inhibitor tenofovir. Overall, we find that HNG-156 is noncytotoxic, has a broad inhibition profile, and provides a positive combination with several inhibitors of the HIV-1 life cycle. These results support the pursuit of efficacy and toxicity analyses in more advanced cell and animal models to develop peptide triazole family inhibitors of HIV-1 into antagonists of HIV-1 infection.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Triazóis
/
HIV-1
/
Inibidores da Fusão de HIV
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos