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Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: e02354-16. doi: 10.1128/AAC.02354-16. Print 2017 May.

Oligonucleotide-Lipid Conjugates Forming G-Quadruplex Structures Are Potent and Pangenotypic Hepatitis C Virus Entry Inhibitors In Vitro and Ex Vivo.

Author information

1
Molecular Virology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
2
Section of Virology, Faculty of Medicine, St. Mary's Campus, Imperial College London, London, United Kingdom.
3
AIDS Research Group, Institut D'Investigacions Biomèdics August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
4
Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) and Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain.
5
Infection Biology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
6
ICREA, Barcelona, Spain.
7
Faculté de Biologie, Sorbonne Universités, UPMC Université Paris 06, Paris, France.
8
Molecular Virology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain juana.diez@upf.edu.

Abstract

A hepatitis C virus (HCV) epidemic affecting HIV-infected men who have sex with men (MSM) is expanding worldwide. In spite of the improved cure rates obtained with the new direct-acting antiviral drug (DAA) combinations, the high rate of reinfection within this population calls urgently for novel preventive interventions. In this study, we determined in cell culture and ex vivo experiments with human colorectal tissue that lipoquads, G-quadruplex DNA structures fused to cholesterol, are efficient HCV pangenotypic entry and cell-to-cell transmission inhibitors. Thus, lipoquads may be promising candidates for the development of rectally applied gels to prevent HCV transmission.

KEYWORDS:

DNA G-quadruplex structures; HCV cell-to-cell inhibitor; HCV entry inhibitor; HCV pangenotypic inhibitor; antiviral treatment; oligonucleotide-cholesterol conjugates

PMID:
28193659
PMCID:
PMC5404530
DOI:
10.1128/AAC.02354-16
[Indexed for MEDLINE]
Free PMC Article

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