title: Zika Virus Genomic RNA Possesses Conserved G-Quadruplexes Characteristic of the Flaviviridae Family.
abstract: Zika virus has emerged as a global concern because neither a 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. The analysis identified >60 PQSs in the Zika genome. To minimize the PQS population, conserved sequences in the Flaviviridae family were found by sequence alignment, identifying seven PQSs in the prM, E, NS1, NS3, and NS5 genes. 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.
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Fleming
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Anton
authors.initials: A
authors.lastname: Alenko
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Burrows
mesh_terms: D017124:Conserved Sequence; D054856:G-Quadruplexes; D016679:Genome, Viral; D023281:Genomics; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics; D000071244:Zika Virus / Q000737:chemistry / Q000145:classification / Q000235:genetics*
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins
keywords: Flaviviridae; G-quadruplex; RNA genome structure; Zika virus