Inhibition of dengue virus infection by small interfering RNAs that target highly conserved sequences in the NS4B or NS5 coding regions

Dengue fever is one of the most common viral infections in the world. Although a vaccine against dengue virus (DENV) has been approved in several countries, this disease is still considered a public health priority worldwide. The ability of three small interfering RNAs (FG-siRNAs) targeting conserved sequences in the NS4B and NS5 regions of the DENV genome to inhibit DENV replication was tested in vitro in both Vero and C6/36 cells. The FG-siRNAs were effective against DENV-1, -3, and -4, but not DENV-2. A fourth siRNA specifically targeting the NS5 region of the DENV-2 genome (SG-siRNA) was designed and tested against two different DENV-2 strains, showing high levels of inhibition in both mammalian and insect cells.