Crystal structure of Zika virus NS5 RNA-dependent RNA polymerase

• DOI: 10.1038/ncomms14764
• Publication Date: 2017-03-27T09:33:53Z
• Authors: Andre S. Godoy; Gustavo M. A. Lima; Ketllyn I. Z. Oli...; Naiara U. Torres; Fernando V. Maluf; Rafael V. C. Guido; Glaucius Oliva
• Keywords: Zika Virus; Flavivirus; RNA virus

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 novel efficacious safe antiviral drugs. Due to its central role in RNA viral replication, non-structural protein 5 (NS5) RNA-dependent RNA-polymerase (RdRp) is prime target for drug discovery. Here we describe crystal structure recombinant ZIKV NS5 RdRp domain at 1.9 Å resolution as platform structure-based design strategy. overall similar other flaviviral homologues. However, priming loop site, which suitable non-nucleoside polymerase inhibitor design, shows significant differences comparison with dengue structures, including tighter pocket modified local charge distribution.