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

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

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Department of Molecular Medicine, University of Padua, Padua, Italy.
Department of Molecular Medicine, University of Padua, Padua, Italy; Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000 Leuven, Belgium.
Department of Molecular Medicine, University of Padua, Padua, Italy. Electronic address:


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.


Antiretroviral drug; Aptamer; Attachment; HIV

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