West Nile virus (WNV) is an enveloped, single-stranded, positive RNA virus belonging to the Flavivirus genus (Flaviviridae family). Different WNV strains have been involved in important outbreaks of human and animal diseases, and WNV infection is now considered an emerging world health problem. Like other RNA viruses, WNV has a compact RNA genome that efficiently stores all the information required for the completion of the infectious cycle. The efficiency of this storage system is attributable to supracoding elements, i.e., discrete, structural units that play essential functions. The information coded in the form of structural elements overlaps and complements the protein coding information and is highly conserved across Flavivirus spp. These elements therefore offer interesting potential targets for novel therapeutic agents. We have applied a SELEX procedure to isolate RNA aptamers against the essential 3’ untranslated region (3’UTR) of the WNV genome. Aptamers are oligonucleotides that efficiently and specifically bind to a ligand molecule. Starting from a theoretical highly sequence-variable population consisting of more than 1018 different molecules, and after six rounds of selection we have identified two main groups of aptamers defined by conserved sequence motifs complementary to highly conserved counter parts within essential structural elements of the WNV genome. Current results point out the potential of these essential functional genomic RNA elements to efficiently bind RNA molecules, therefore to be involved in RNA-RNA interactions, offering a potential of being used as targets of antiviral agents based on nucleic acids. Further biochemical and functional studies are being performed to characterize the antiviral activity of identified RNA aptamers.