Zika virus has emerged as a global concern because neither an effective vaccine nor antiviral compounds targeting it exist. A structure for the positive-sense RNA genome has not been established, leading us to look for potential G-quadruplex sequences (PQS) in the genome. Conserved sequences in the <i>Flaviviridae</i> family were found by sequence alignment, identifying seven PQSs in the prM, E, NS1, NS3, and NS5 genes of ZIKV. Next, alignment of 78 Zika strain genomes identified a unique PQS near the end of the 3`-UTR. Structural studies on the G-quadruplex sequences found four of the conserved Zika virus sequences to adopt stable, parallel-stranded folds that bind a G-quadruplex-specific compound, and one that was studied caused polymerase stalling when folded to a G-quadruplex. Targeting these PQSs with G-quadruplex binding molecules validated in previous clinical trials may represent a new approach for inhibiting viral replication. Studies of the impact of PQSs on polymerase activity will be presented.

Targeting G-quadruplexes in the Zika virus RNA genome

255th National Meeting (2018)

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