CD4-BFFI: a novel, bifunctional HIV-1 entry inhibitor with high and broad antiviral potency.
Antiviral Res
; 83(3): 257-66, 2009 Sep.
Article
en En
| MEDLINE
| ID: mdl-19559732
ABSTRACT
Resistance to antiretroviral drugs is a common problem in the treatment of HIV-1-infected patients. To overcome resistance, we generated a novel, bifunctional HIV-1 entry inhibitor by combining the anti-CD4 monoclonal antibody (mAb) 6314 with a fusion inhibitor similar to T-651 (anti-CD4 mAb based BiFunctional Fusion Inhibitor, CD4-BFFI). CD4-BFFI has potent antiviral activity against a multitude of HIV-1 isolates independent of their co-receptor usage and genetic background. It has higher antiviral potency compared to the fusion inhibitor T-651 or the anti-CD4 mAb 6314 used independently. More importantly, every HIV-1 strain tested was fully inhibited by CD4-BFFI while many strains were only partially inhibited by 6314. CD4-BFFI also retained antiviral potency against virus strains resistant to two fusion inhibitors, a CCR5 antagonist and an anti-CCR5 mAb. Pre-incubation of cells with a saturating concentration of anti-CD4 mAbs reduced the antiviral potency of CD4-BFFI, suggesting that binding of CD4-BFFI to the cell surface via its CD4 mAb portion is required for the antiviral potency of its fusion inhibitor moiety. Collectively, we present a novel HIV-1 inhibitor with a dual mode of action and excellent antiviral potency against wildtype and entry-inhibitor resistant virus strains suggesting that CD4-BFFI may have a high barrier to resistance.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Antígenos CD4
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VIH-1
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Inhibidores de Fusión de VIH
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Anticuerpos Monoclonales
Límite:
Humans
Idioma:
En
Año:
2009
Tipo del documento:
Article