Structure of the yellow fever NS5 protein reveals conserved drug targets shared among flaviviruses
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
31202975
DOI
10.1016/j.antiviral.2019.104536
PII: S0166-3542(19)30211-6
Knihovny.cz E-resources
- Keywords
- Crystal structure, Drug design, Flavivirus, Polymerase, RNA, Yellow fever,
- MeSH
- Dengue MeSH
- Disease Outbreaks MeSH
- Zika Virus Infection MeSH
- Protein Conformation MeSH
- Methyltransferases chemistry MeSH
- Models, Molecular MeSH
- Primates MeSH
- Protein Domains MeSH
- Drug Design MeSH
- Virus Replication drug effects MeSH
- RNA-Dependent RNA Polymerase chemistry MeSH
- Yellow Fever Vaccine MeSH
- Binding Sites MeSH
- Viral Nonstructural Proteins chemistry drug effects genetics MeSH
- Yellow fever virus drug effects genetics metabolism MeSH
- Zinc MeSH
- Yellow Fever virology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Methyltransferases MeSH
- RNA-Dependent RNA Polymerase MeSH
- Yellow Fever Vaccine MeSH
- Viral Nonstructural Proteins MeSH
- Zinc MeSH
Yellow fever virus (YFV) is responsible for devastating outbreaks of Yellow fever (YF) in humans and is associated with high mortality rates. Recent large epidemics and epizootics and exponential increases in the numbers of YF cases in humans and non-human primates highlight the increasing threat YFV poses, despite the availability of an effective YFV vaccine. YFV is the first human virus discovered, but the structures of several of the viral proteins remain poorly understood. Here we report the structure of the full-length NS5 protein, a key enzyme for the replication of flaviviruses that contains both a methyltransferase domain and an RNA dependent RNA polymerase domain, at 3.1 Å resolution. The viral polymerase adopts right-hand fold, demonstrating the similarities of the Yellow fever, Dengue and Zika polymerases. Together this data suggests NS5 as a prime and ideal target for the design of pan-flavivirus inhibitors.
References provided by Crossref.org
Structural basis for broad-spectrum binding of AT-9010 to flaviviral methyltransferases
The Present and Future of Virology in the Czech Republic-A New Phoenix Made of Ashes?
A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases
High-Throughput Fluorescent Assay for Inhibitor Screening of Proteases from RNA Viruses
Structural analysis of the putative SARS-CoV-2 primase complex
