Oligonucleotide-lipid conjugates forming G-quadruplex structures are potent and pangenotypic hepatitis C virus entry inhibitors in vitro and ex vivo

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. ; The authors are supported by grants BFU2013-44629-R (to JD, GK and APL), and SAF2013-46077-R (to AM), and also through the “María de Maeztu” Programme for Units of Excellence in R&D (MDM-2014-0370), all from the Spanish Ministry of Economy and Competitiveness and FEDER. Work at Imperial College (CH) was funded by EC FP7 grant 305578 (PathCO).