The G-quadruplex-forming aptamer AS1411 potently inhibits HIV-1 attachment to the host cell

Int J Antimicrob Agents. 2016 Apr;47(4):311-6. doi: 10.1016/j.ijantimicag.2016.01.016. Epub 2016 Mar 11.


AS1411 is a G-rich aptamer that forms a stable G-quadruplex structure and displays antineoplastic properties both in vitro and in vivo. This oligonucleotide has undergone phase 2 clinical trials. The major molecular target of AS1411 is nucleolin (NCL), a multifunctional nucleolar protein also present in the cell membrane where it selectively mediates the binding and uptake of AS1411. Cell-surface NCL has been recognised as a low-affinity co-receptor for human immunodeficiency virus type 1 (HIV-1) anchorage on target cells. Here we assessed the anti-HIV-1 properties and underlying mechanism of action of AS1411. The antiviral activity of AS1411 was determined towards different HIV-1 strains, host cells and at various times post-infection. Acutely, persistently and latently infected cells were tested, including HIV-1-infected peripheral blood mononuclear cells from a healthy donor. Mechanistic studies to exclude modes of action other than virus binding via NCL were performed. AS1411 efficiently inhibited HIV-1 attachment/entry into the host cell. The aptamer displayed antiviral activity in the absence of cytotoxicity at the tested doses, therefore displaying a wide therapeutic window and favourable selectivity indexes. These findings, besides validating cell-surface-expressed NCL as an antiviral target, open the way for the possible use of AS1411 as a new potent and promisingly safe anti-HIV-1 agent.

Keywords: Antiretroviral drug; Aptamer; Attachment; HIV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / toxicity
  • Aptamers, Nucleotide
  • Cell Survival / drug effects
  • Cells, Cultured
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / virology
  • Oligodeoxyribonucleotides / pharmacology*
  • Oligodeoxyribonucleotides / toxicity
  • Virus Attachment / drug effects*


  • AGRO 100
  • Anti-HIV Agents
  • Aptamers, Nucleotide
  • Oligodeoxyribonucleotides