Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 75, Issue 10, Pages 1723-1736Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-018-2751-x
Keywords
Viral replication; Flavivirus; Non-structural protein 5; RNA capping; Pathogen-host interaction; Drug discovery; Antiviral inhibitors
Categories
Funding
- March of Dimes Foundation [1-FY15-345]
- Kimmel Scholar Award from Sidney Kimmel Foundation for Cancer Research
- NIH [1R35GM119721]
- Trans fund of state of California [AB2664]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available