Phylogenetically based establishment of a dengue virus panel, representing all available genotypes, as a tool in dengue drug discovery

Publication date: Available online 11 May 2019Source: Antiviral ResearchAuthor(s): Franck Touret, Cécile Baronti, Olivia Goethals, Marnix Van Loock, Xavier de Lamballerie, Gilles QueratAbstractDengue fever is the most widespread of the human arbovirus diseases, with approximately one third of the world's population at risk of infection. Dengue viruses are members of the genus Flavivirus (family Flaviviridae) and, antigenically, they separate as four closely related serotypes (1–4) that share 60–75% amino acid homology. This genetic diversity complicates the process of antiviral drug discovery. Thus, currently no approved dengue-specific therapeutic treatments are available. With the aim of providing an efficient tool for dengue virus drug discovery, a collection of nineteen dengue viruses, representing the genotypic diversity within the four serotypes, was developed. After phylogenetic analysis of the full-length genomes, we selected relevant strains from the EVAg collection at Aix-Marseille University and completed the virus collection, using a reverse genetic system based on the infectious sub-genomic amplicons technique. Finally, we evaluated this dengue virus collection against three published dengue inhibitory compounds. NITD008, which targets the highly conserved active site of the viral NS5 polymerase enzyme, exhibited similar antiviral potencies against each of the different dengue genotypes in the panel. Compounds targeting less conserved protein subdomains, suc...
Source: Antiviral Therapy - Category: Virology Source Type: research