Inhibition of HIV-1 infectivity by zinc-ejecting aromatic C-nitroso compounds View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1993-02

AUTHORS

William G. Rice, Catherine A. Schaeffer, Brad Harten, Francois Villinger, Terri L. South, Michael F. Summers, Louis E. Henderson, Julian W. Bess, Larry O. Arthur, J. Steven McDougal, Sherry L. Orloff, Jerome Mendeleyev, Ernest Kun

ABSTRACT

Retroviral nucleocapsid and gag-precursor proteins from all known strains of retroviruses contain one or two copies of an invariant sequence, Cys-X2-Cys-X4-His-X4-Cys, that is populated with zinc in mature particles. Modification of cysteine or histidine residues results in defective packaging of genomic viral RNA and formation of non-infectious particles, making these structures potentially attractive targets for antiviral therapy. We recently reported that aromatic C-nitroso ligands of poly(ADP-ribose) polymerase preferentially destabilize one of the two (Cys-X2-Cys-X28-His-X2-Cys) zinc-fingers with concomitant loss of enzymatic activity, coincidental with selective cytocidal action of the C-nitroso substituted ligands on cancer cells. Based on the occurrence of (3Cys, 1His) zinc-binding sites in both retroviral nucleocapsid and gag proteins and in poly(ADP-ribose) polymerase, we reasoned that the C-nitroso compounds may also have antiretroviral effects. We show here that two such compounds, 3-nitrosobenzamide and 6-nitroso-1,2-benzopyrone, inhibit infection of human immunodeficiency virus HIV-1 in human lymphocytes and also eject zinc from isoalted HIV-1 nucleocapsid zinc fingers and from intact HIV-1 virions. Thus the design of zinc-ejecting agents that target retroviral zinc fingers represents a new approach to the chemotherapy of AIDS. More... »

PAGES

473-475

Journal

TITLE

Nature

ISSUE

6411

VOLUME

361

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/361473a0

    DOI

    http://dx.doi.org/10.1038/361473a0

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/8429889


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