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

Sci Rep. 2018 Sep 6;8(1):13342. doi: 10.1038/s41598-018-31513-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacology
  • Cell Line
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • HIV-1* / chemistry
  • HIV-1* / metabolism
  • Humans
  • Nickel* / chemistry
  • Nickel* / pharmacology
  • RNA, Viral* / metabolism
  • Regulatory Sequences, Ribonucleic Acid*
  • Rubidium* / chemistry
  • Rubidium* / pharmacology
  • tat Gene Products, Human Immunodeficiency Virus* / chemistry
  • tat Gene Products, Human Immunodeficiency Virus* / metabolism

Substances

  • Antiviral Agents
  • Coordination Complexes
  • RNA, Viral
  • Regulatory Sequences, Ribonucleic Acid
  • tat Gene Products, Human Immunodeficiency Virus
  • Nickel
  • Rubidium