Details

Autor(en) / Beteiligte

• Touret, Franck
• Baronti, Cécile
• Goethals, Olivia
• Van Loock, Marnix
• de Lamballerie, Xavier
• Querat, Gilles

Titel

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

Ist Teil von

• Antiviral research, 2019-08, Vol.168, p.109-113

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Dengue 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, such as the capsid inhibitor ST-148, or SDM25N, a ∂ opioid receptor antagonist which indirectly targets NS4B, exhibited larger differences in potency against the various genotypes of dengue viruses. These results illustrate the importance of a phylogenetically based dengue virus reference panel for dengue antiviral research. The collection developed in this study, which includes such representative dengue viruses, has been made available to the scientific community through the European Virus Archive to evaluate novel DENV antiviral candidates. •A phylogenetic-based selection of a representative panel of dengue genotypes.•Non-available biological strains were produced, from NCBI sequences, using reverse genetic method “ISA”.•Three already characterised antiviral compounds were tested against this panel of 19 dengue viruses.•Two compounds exhibited large differences in potency, highlighting the importance of using large panel of dengue genotypes.