title: A novel anticancer agent ARC antagonizes HIV-1 and HCV.
abstract: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) pose major public health concerns worldwide. HCV is clearly associated with the occurrence of hepatocellular carcinoma, and recently HIV infection has also been linked to the development of a multitude of cancers. Previously, we identified a novel nucleoside analog transcriptional inhibitor ARC (4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-pyrrolo[2,3-d]-pyrimidine-5-carboxamide) that exhibited proapoptotic and antiangiogenic properties in vitro. Here, we evaluated the effect of ARC on HIV-1 transcription and HCV replication. Using reporter assays, we found that ARC inhibited HIV-1 Tat-based transactivation in different cell systems. Also, using hepatoma cells that harbor subgenomic and full-length replicons of HCV, we found that ARC inhibited HCV replication. Together, our data indicate that ARC could be a promising candidate for the development of antiviral therapeutics against HIV and HCV.
authors.affiliation: Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, USA. snekhai@howard.edu
authors.forename: S
authors.initials: S
authors.lastname: Nekhai
authors.forename: U G
authors.initials: UG
authors.lastname: Bhat
authors.forename: T
authors.initials: T
authors.lastname: Ammosova
authors.forename: S K
authors.initials: SK
authors.lastname: Radhakrishnan
authors.forename: M
authors.initials: M
authors.lastname: Jerebtsova
authors.forename: X
authors.initials: X
authors.lastname: Niu
authors.forename: A
authors.initials: A
authors.lastname: Foster
authors.forename: T J
authors.initials: TJ
authors.lastname: Layden
authors.forename: A L
authors.initials: AL
authors.lastname: Gartel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017930:Genes, Reporter; D015497:HIV-1 / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D009705:Nucleosides / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: C509961:4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-pyrrolo(2,3-d)-pyrimidine-5-carboxamide; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D009705:Nucleosides; D011743:Pyrimidines