A novel anticancer agent ARC antagonizes HIV-1 and HCV.
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.
Nekhai
S
S
Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, USA. snekhai@howard.edu
Bhat
U G
UG
Ammosova
T
T
Radhakrishnan
S K
SK
Jerebtsova
M
M
Niu
X
X
Foster
A
A
Layden
T J
TJ
Gartel
A L
AL
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*
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