ChemMedChem

Cover image for Vol. 12 Issue 14

Editorial Board Chairs: Karl-Heinz Altmann, Antonello Mai, Rainer Metternich. Editor: David Peralta

Impact Factor: 3.225

ISI Journal Citation Reports © Ranking: 2016: 17/60 (Chemistry Medicinal); 73/256 (Pharmacology & Pharmacy)

Online ISSN: 1860-7187

Associated Title(s): Angewandte Chemie International Edition, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemBioChem, Medicinal Research Reviews, Molecular Informatics

July 05, 2011

VIP: Cell-Free HIV-1 Virucidal Action by Modified Peptide Triazole Inhibitors of Env gp120

VIP: Cell-Free HIV-1 Virucidal Action by Modified Peptide Triazole Inhibitors of Env gp120Arangassery Rosemary Bastian, Kantharaju, Karyn McFadden, Caitlin Duffy, Srivats Rajagopal, Mark R. Contarino, Elisabeth Papazoglou, and Irwin Chaiken*

The initial entry of HIV-1 into host cells remains a compelling yet elusive target for the development of agents to prevent infection, a critical need in the fight against the global AIDS epidemic. A collaborative research group at Drexel University and Drexel University College of Medicine (Philadelphia, PA, USA) has demonstrated the ability of modified peptide triazole inhibitors that specifically target the HIV-1 envelope (Env) protein gp120 to physically disrupt virus particles in the absence of host cells. Peptide triazole inhibitors bind to Env with high affinity, suppress interactions of Env at its host cell receptor binding sites, and inhibit cell infection by a broad range of virus subtypes. These inhibitors appear to function by entrapping the intrinsically metastable Env protein into an inactivated structure. This conformational entrapment effectively halts the entry process at the initial stages of virus–cell encounter.

Chaiken and colleagues found that under conditions similar to those at which a newly designed peptide triazole “KR13” inhibits infection of host cells by an HIV-1 pseudovirus, it also causes virus rupture and release of an internal HIV-1 protein called gag p24 when incubated with virus alone. Both inhibition of cell infection and p24 release are enhanced substantially by the multivalent display of KR13 on gold nanoparticles. The novel antagonist design and characterization results of this work could lead to the creation of a virucide to suppress initial HIV-1 infection, viremia in infected individuals, and spread of infection from infected to uninfected individuals. Such agents could be used for HIV-1 microbicides and therapeutics. The group's results also suggest that ligand-specific pathogen rupture may be possible for other viruses such as influenza, Ebola, and Dengue, which contain metastable prefusion surface protein complexes.

Received April 6, 2011; published online June 28, 2011, DOI: 10.1002/cmdc.201100177.

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