Targeting a genomic RNA G-quadruplex of dengue virus with small molecules as an alternative to protein-targeted therapeutics - PubMed
3 hours ago
- #RNA G-quadruplex
- #Dengue Virus Antiviral
- #BRACO-19
- The study investigates targeting RNA G-quadruplexes (G4s) in the dengue virus (DENV) genome as an alternative to protein-targeted antiviral therapies.
- Bioinformatic and biophysical analyses identified conserved G4-forming sequences across all DENV serotypes, with BRACO-19 showing high stabilizing effects, particularly on the G4-3 region in the NS3 gene.
- BRACO-19 treatment significantly reduced viral translation and demonstrated strong antiviral effects in a mouse model of DENV infection, with broad-spectrum activity against all serotypes.
- A recombinant DENV with a mutated G4-3 region showed enhanced gene expression and reduced sensitivity to BRACO-19, confirming RNA G4s as druggable targets.
- The approach offers potential to overcome mutational escape and serotype variability, paving the way for broad-spectrum antivirals against flaviviruses.