Cellular and Molecular Life Sciences

, Volume 75, Issue 10, pp 1723–1736 | Cite as

Structure and function of Zika virus NS5 protein: perspectives for drug design

  • Boxiao Wang
  • Stephanie Thurmond
  • Rong Hai
  • Jikui Song


Zika virus (ZIKV) belongs to the positive-sense single-stranded RNA-containing Flaviviridae family. Its recent outbreak and association with human diseases (e.g. neurological disorders) have raised global health concerns, and an urgency to develop a therapeutic strategy against ZIKV infection. However, there is no currently approved antiviral against ZIKV. Here we present a comprehensive overview on recent progress in structure–function investigation of ZIKV NS5 protein, the largest non-structural protein of ZIKV, which is responsible for replication of the viral genome, RNA capping and suppression of host interferon responses. Structural comparison of the N-terminal methyltransferase domain and C-terminal RNA-dependent RNA polymerase domain of ZIKV NS5 with their counterparts from related viruses provides mechanistic insights into ZIKV NS5-mediated RNA replication, and identifies residues critical for its enzymatic activities. Finally, a collection of recently identified small molecule inhibitors against ZIKV NS5 or its closely related flavivirus homologues are also discussed.


Viral replication Flavivirus Non-structural protein 5 RNA capping Pathogen–host interaction Drug discovery Antiviral inhibitors 



This work was supported by March of Dimes Foundation (1-FY15-345), Kimmel Scholar Award from Sidney Kimmel Foundation for Cancer Research and NIH (1R35GM119721) to J.S. This work is also partly funded by Trans fund of state of California (AB2664) to J.S. and R.H.


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of BiochemistryUniversity of CaliforniaRiversideUSA
  2. 2.Department of Microbiology and Plant Pathology University of CaliforniaRiversideUSA

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