Closing two doors of viral entry: Intramolecular combination of a coreceptor- and fusion inhibitor of HIV-1Report as inadecuate




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Virology Journal

, 5:56

First Online: 01 May 2008Received: 25 March 2008Accepted: 01 May 2008

Abstract

We describe a novel strategy in which two inhibitors of HIV viral entry were incorporated into a single molecule. This bifunctional fusion inhibitor consists of an antibody blocking the binding of HIV to its co-receptor CCR5, and a covalently linked peptide which blocks envelope mediated virus-cell fusion. This novel bifunctional molecule is highly active on CCR5- and X4-tropic viruses in a single cycle assay and a reporter cell line with IC50 values of 0.03–0.05 nM. We demonstrated that both inhibitors contribute to the antiviral activity. In the natural host peripheral blood mononuclear cells PBMC the inhibition of CXCR4-tropic viruses is dependant on the co-expression of CCR5 and CXCR4 receptors. This bifunctional inhibitor may offer potential for improved pharmacokinetic parameters for a fusion inhibitor in humans and the combination of two active antiviral agents in one molecule may provide better durability in controlling the emergence of resistant viruses.

AbbreviationsBFFIbifunctional entry inhibitor

HIV-1human immunodeficiency virus type 1

HAARThighly active antiretroviral therapy

FIfusion inhibitor

Electronic supplementary materialThe online version of this article doi:10.1186-1743-422X-5-56 contains supplementary material, which is available to authorized users.

Erhard Kopetzki, Andreas Jekle contributed equally to this work.

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Author: Erhard Kopetzki - Andreas Jekle - Changhua Ji - Eileen Rao - Jun Zhang - Stephan Fischer - Nick Cammack - Surya Sankuratri

Source: https://link.springer.com/







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