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Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo.

ABSTRACT: Shape-selective recognition of nucleic acid structures by supramolecular drugs offers the potential to treat disease. The Trans Activation Response (TAR) region is a region of high secondary structure within the human immunodeficiency virus-1 (HIV-1) RNA that complexes with the virus-encoded Transactivator protein (TAT) and regulates viral transcription. Herein, we explore different metallo-supramolecular triple stranded helicates (cylinders) that target the TAR bulge motif and inhibit the formation of TAR-TAT complexes and HIV infection. Cylinders that incorporate Ni(II) and Ru(II) showed the most potent anti-viral activity with limited evidence of cellular cytotoxicity. These metallo-supramolecular compounds provide an exciting avenue for developing a new class of anti-viral agents.

SUBMITTER: Cardo L

PROVIDER: S-EPMC6127258 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo.

Cardo Lucia L Nawroth Isabel I Cail Peter J PJ McKeating Jane A JA Hannon Michael J MJ

Scientific reports 20180906 1

Shape-selective recognition of nucleic acid structures by supramolecular drugs offers the potential to treat disease. The Trans Activation Response (TAR) region is a region of high secondary structure within the human immunodeficiency virus-1 (HIV-1) RNA that complexes with the virus-encoded Transactivator protein (TAT) and regulates viral transcription. Herein, we explore different metallo-supramolecular triple stranded helicates (cylinders) that target the TAR bulge motif and inhibit the forma ...[more]

PMID: 30190568

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