Crystal structure of Zika virus NS5 RNA-dependent RNA polymerase

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-struc...

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Bibliographic Details
Published in:Nature communications 2017-03, Vol.8 (1), p.14764-14764, Article 14764
Main Authors: Godoy, Andre S., Lima, Gustavo M. A., Oliveira, Ketllyn I. Z., Torres, Naiara U., Maluf, Fernando V., Guido, Rafael V. C., Oliva, Glaucius
Format: Article
Language:English
Subjects:
631/154/51
631/45/535/1266
Antiviral Agents - pharmacology
Catalytic Domain
Crystal structure
Crystallography, X-Ray
Data collection
Dengue fever
Drug Discovery
Humanities and Social Sciences
Kinases
Ligands
multidisciplinary
Protein Conformation
Proteins
Recombination, Genetic
RNA polymerase
RNA Replicase - chemistry
Science
Science (multidisciplinary)
Viral Nonstructural Proteins - chemistry
West Nile virus
Zika virus
Zika Virus - drug effects
Zika Virus - enzymology
Zika Virus - genetics
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Summary: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. The Zika virus outbreak is a global health threat and there is an urgent need for drugs against the virus. Here the authors present the structure of the RNA-dependent RNA-polymerase domain from Zika non-structural protein 5, which is a template for the design of non-nucleoside polymerase inhibitors.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms14764