Conserved Sequences from Dengue Virus Genomes Form\nStable G‑Quadruplexes

Arthropod-borne members\nof the genus <i>Orthoflavivirus</i> cause significant human\ndisease. Four serotypes of dengue virus\nare endemic globally, and approximately 50 percent of the world’s\npopulation lives in a dengue-affected area. Complications from immunoenhancement\noccurring after a secondary infection with a different dengue serotype\nmake vaccine development challenging. Antiviral therapies that target\nfeatures conserved in all four serotypes would, therefore, be beneficial.\nComputational studies identified multiple potential G-quadruplex sites\nthat are conserved in the RNA genome sequences of members of the genus <i>Orthoflavivirus</i>. Biophysical studies confirmed that the\nNS5-B quadruplex sequences obtained from viruses of each dengue serotype\ncan form quadruplexes <i>in vitro</i>, and binding data\nshowed that known quadruplex binders stabilized NS5-B quadruplexes\nfor all four dengue serotypes.