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.