Flaviviridae is a family of RNA viruses that includes numerous important human and animal pathogens. Recent studies on subgenomic flaviviridae replicons have revealed that the non-structural (NS) proteins, which are encoded by the C-terminal part of the polyprotein, play a crucial role in viral RNA replication. Accordingly, these proteins are assumed to form replication complexes in conjunction with genomic RNA and possibly with other cellular factors. One the most important non-structural enzymes that plays a key role in the life cycle of flaviviridae viruses is the viral helicase. Sequence alignments of the viral helicases from this family identified several conserved sequence motifs that are important for biological functions. Herein, an effort is made to summarize the current epidemics associated with the flaviviridae family worldwide, the potential of helicase enzymes as a promising pharmacological target and the use of nucleoside analogs as simple, efficient and rather versatile antiviral agents
