Conserved Sequences from Dengue Virus Genomes Form Stable G‑Quadruplexes

Arthropod-borne members
of the genus Orthoflavivirus cause significant human
disease. Four serotypes of dengue virus
are endemic globally, and approximately 50 percent of the world’s
population lives in a dengue-affected area. Complications from immunoenhancement
occurring after a secondary infection with a different dengue serotype
make vaccine development challenging. Antiviral therapies that target
features conserved in all four serotypes would, therefore, be beneficial.
Computational studies identified multiple potential G-quadruplex sites
that are conserved in the RNA genome sequences of members of the genus Orthoflavivirus. Biophysical studies confirmed that the
NS5-B quadruplex sequences obtained from viruses of each dengue serotype
can form quadruplexes in vitro, and binding data
showed that known quadruplex binders stabilized NS5-B quadruplexes
for all four dengue serotypes.