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

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作者：
Lucia Cardo
Isabel Nawroth
Peter J. Cail
Jane A. McKeating
Michael J. Hannon
机构：
[1] University of Birmingham,School of Chemistry
[2] Edgbaston,Institute of Immunology and Immunotherapy Centre for Human Virology
[3] University of Birmingham,Nuffield Department of Medicine
[4] Edgbaston,undefined
[5] Oxford University,undefined
来源：
Scientific Reports | / 8卷
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摘要：
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.
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