Extended dengue virus panel: application to antiviral compounds studies

Dengue is the most widespread arboviral disease with approximately 1/3 of the world population at risk. Dengue viruses belong to the genus Flavivirus (Flaviviradea family) and are divided into four closely related serotypes (1-4) that share 60 to 75 % identity at the amino acid level. This viral diversity complicates the development of antivirals and currently they are still no approved treatment. With the aim of providing an efficient tool for dengue virus research particularly to evaluated compounds efficacy, we developed a panel of 19 dengue viruses covering nearly all genotypes in the four serotypes. After a phylogenetic analysis we selected relevant strains from our collection and design reverse genetic system based on the ISA technic to generate the missing ones. Finally, we evaluated our dengue panel against three, already published, compounds. We demonstrated that NITD008, which targeted the very conserved active site of the polymerase, exhibited very similar EC50s regardless of the dengue genotypes. But compounds targeting either directly or indirectly less conserved proteins such as the capsid (ST-148) or NS4B (SDM25N) exhibited large differences of activity toward the various genotypes of dengue viruses. These data reinforce our conviction that there is a real need to evaluate compounds activity against a large panel of dengue viruses.