Crystal structure of Zika virus NS5 RNA-dependent RNA polymerase

Author(s)

Godoy, Andre S. ; Lima, Gustavo M. A. ; Oliveira, Ketllyn I. Z. ; Torres, Naiara U. ; Maluf, Fernando V. ; Guido, Rafael V. C. ; Oliva, Glaucius

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 8, MAR 27 2017.
• Web of Science Citations: 42

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 angstrom 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. (AU)

• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 16/17153-2 - Structural biology and drug development against the protein NS5 Zika virus
• Grantee: Ketllyn Irene Zagato de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 15/16811-3 - Multi-user equipament aproved in grant 2014:15546-1: crystallization robot Gryphon
• Grantee: Richard Charles Garratt
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 16/19712-9 - Structural characterization of Zika virus proteins and search for antiviral agents
• Grantee: Andre Schutzer de Godoy
• Support Opportunities: Scholarships in Brazil - Post-Doctoral