An in vitro method to conduct genomic replication of the viral genomes of
viruses that utilize RNA-dependent RNA polymerase for replication (RDRP
viruses), such as HCV. The method employs a construct comprising the 3'
and 5' untranslated regions (UTRs) of the viral genome which are operably
linked on the 5' and 3' ends of a reporter sequence, in antisense
orientation, such that when viral replication is occurring within the cell
which produces RDRP, the reporter protein will be made. The method of the
invention provides an efficient means for measuring genomic replication in
RDRP viruses, and also for the rapid screening of compounds for their
ability to inhibit genomic replication of RDRP viruses, including the
Hepatitis C virus (HCV).