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

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

External organisations

  • School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. r.l.johnston@bham.ac.uk.
  • Institute of Immunology and Immunotherapy Centre for Human Virology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
  • Nuffield Department of Medicine, Oxford University, Oxford, OX3 7BN, UK. jane.mckeating@ndm.ox.ac.uk.
  • School of Chemistry, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. m.j.hannon@bham.ac.uk.

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.

Details

Original languageEnglish
Article number13342
JournalScientific Reports
Volume8
Issue number1
Publication statusPublished - 6 Sep 2018