title: Crystal structure of Zika virus NS5 RNA-dependent RNA polymerase.
abstract: The current Zika virus (ZIKV) outbreak became a global health threat of complex epidemiology and devastating neurological impacts, therefore requiring urgent efforts towards the development of novel efficacious and safe antiviral drugs. Due to its central role in RNA viral replication, the non-structural protein 5 (NS5) RNA-dependent RNA-polymerase (RdRp) is a prime target for drug discovery. Here we describe the crystal structure of the recombinant ZIKV NS5 RdRp domain at 1.9 Å resolution as a platform for structure-based drug design strategy. The overall structure is similar to other flaviviral homologues. However, the priming loop target site, which is suitable for non-nucleoside polymerase inhibitor design, shows significant differences in comparison with the dengue virus structures, including a tighter pocket and a modified local charge distribution.
authors.affiliation: Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100-Jardim Santa Angelina, São Carlos 13563-120, Brazil.
authors.forename: Andre S
authors.initials: AS
authors.lastname: Godoy
authors.affiliation: Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100-Jardim Santa Angelina, São Carlos 13563-120, Brazil.
authors.forename: Gustavo M A
authors.initials: GM
authors.lastname: Lima
authors.affiliation: Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100-Jardim Santa Angelina, São Carlos 13563-120, Brazil.
authors.forename: Ketllyn I Z
authors.initials: KI
authors.lastname: Oliveira
authors.affiliation: Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100-Jardim Santa Angelina, São Carlos 13563-120, Brazil.|Cellco Biotec, R. Alberto Lanzoni, 993-Parque Santa Felicia, São Carlos 13562-390, Brazil.
authors.forename: Naiara U
authors.initials: NU
authors.lastname: Torres
authors.affiliation: Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100-Jardim Santa Angelina, São Carlos 13563-120, Brazil.|Cellco Biotec, R. Alberto Lanzoni, 993-Parque Santa Felicia, São Carlos 13562-390, Brazil.
authors.forename: Fernando V
authors.initials: FV
authors.lastname: Maluf
authors.affiliation: Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100-Jardim Santa Angelina, São Carlos 13563-120, Brazil.
authors.forename: Rafael V C
authors.initials: RV
authors.lastname: Guido
authors.affiliation: Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100-Jardim Santa Angelina, São Carlos 13563-120, Brazil.
authors.forename: Glaucius
authors.initials: G
authors.lastname: Oliva
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D011487:Protein Conformation; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry*; D011995:Recombination, Genetic; D017361:Viral Nonstructural Proteins / Q000737:chemistry*; D000071244:Zika Virus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics
chemical_list: D000998:Antiviral Agents; C096041:NS5 protein, flavivirus; D017361:Viral Nonstructural Proteins; D012324:RNA-Dependent RNA Polymerase