ArticleThe Journal of biological chemistry2010
Structural and functional analyses of a conserved hydrophobic pocket of flavivirus methyltransferase.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- Development in the Inhibition of Dengue Proteases as Drug Targets.Current medicinal chemistry · 2024Review
- A universal fluorescence polarization high throughput screening assay to target the SAM-binding sites of SARS-CoV-2 and other viral methyltransferases.Emerging microbes & infections · 2023Article
- Structural and functional basis of low-affinity SAM/SAH-binding in the conserved MTase of the multi-segmented Alongshan virus distantly related to canonical unsegmented flaviviruses.PLoS pathogens · 2023Article
- Broad-Spectrum Small-Molecule Inhibitors Targeting the SAM-Binding Site of Flavivirus NS5 Methyltransferase.ACS infectious diseases · 2023Article
- Review
- Preparing for the next viral threat with broad-spectrum antivirals.The Journal of clinical investigation · 2023Review
- Chemical biology and medicinal chemistry of RNA methyltransferases.Nucleic acids research · 2022Article
- Review
- Identification and Characterization of Zika Virus NS5 Methyltransferase Inhibitors.Frontiers in cellular and infection microbiology · 2021Article
- Genomewide Analysis of Mode of Action of themSystems · 2019Article
- Structure and function of Zika virus NS5 protein: perspectives for drug design.Cellular and molecular life sciences : CMLS · 2018Review
- Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond.Nature reviews. Drug discovery · 2017Review
- Toward the identification of viral cap-methyltransferase inhibitors by fluorescence screening assay.Antiviral research · 2017Article
- Dengue Virus Non-Structural Protein 5.Viruses · 2017Review
- The crystal structure of Zika virus NS5 reveals conserved drug targets.The EMBO journal · 2017Article
- Possible Roles of New Mutations Shared by Asian and American Zika Viruses.Molecular biology and evolution · 2017Article
- An Overview of Current Approaches Toward the Treatment and Prevention of West Nile Virus Infection.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Identification and Characterization of Novel Broad-Spectrum Inhibitors of the Flavivirus Methyltransferase.ACS infectious diseases · 2015Article
- 5'-Silylated 3'-1,2,3-triazolyl Thymidine Analogues as Inhibitors of West Nile Virus and Dengue Virus.Journal of medicinal chemistry · 2015Article
- Refolding of a fully functional flavivirus methyltransferase revealed that S-adenosyl methionine but not S-adenosyl homocysteine is copurified with flavivirus methyltransferase.Protein science : a publication of the Protein Society · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The flavivirus methyltransferase (MTase) sequentially methylates the N7 and 2'-O positions of the viral RNA cap (GpppA-RNA → m(7)GpppA-RNA → m(7)GpppAm-RNA), using S-adenosyl-l-methionine (AdoMet) as a methyl donor. We report here that sinefungin (SIN), an AdoMet analog, inhibits several flaviviruses through suppression of viral MTase. The crystal structure of West Nile virus MTase in complex with SIN inhibitor at 2.0-Å resolution revealed a flavivirus-conserved hydrophobic pocket located next to the AdoMet-binding site. The pocket is functionally critical in the viral replication and cap methylations. In addition, the N7 methylation efficiency was found to correlate with the viral replication ability. Thus, SIN analogs with modifications that interact with the hydrophobic pocket are potential specific inhibitors of flavivirus MTase.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.