Flavivirus genome replication involves synthesis of a negative-sense template strand by the RNA-dependent RNA polymerase (RdRp; NS5 pol ) from which additional genome-sense strands are transcribed. This process is controlled by numerous RNA-RNA and RNA-protein interactions determined by virus RNA sequence motifs and secondary structures, called cis-acting replication *To whom correspondence should be addressed. Tel: +44 0118 378 6368; Fax +44 (0)118 378 6537; Email: t.s.gritsun@reading.ac.uk elements (CRE), mapped to the 5 0 -and 3 0 -untranslated regions (UTR) that flank the single open reading frame (ORF) of the genome (9) (10) (11) (12) (13) (14) (15) .