ArticlePLoS pathogens2020
A conformation-based intra-molecular initiation factor identified in the flavivirus RNA-dependent RNA polymerase.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 40 citations in OpenAlex.
- Article
- Well-Tempered Metadynamic Simulations Provide Insights and Leads for Designing Effective Allosteric Inhibitors against SARS-CoV-2 RNA-Dependent RNA Polymerase.Journal of chemical information and modeling · 2025Article
- ZNF33B facilitates Japanese encephalitis virus replication by controlling HSPB1/8-mediated SUMOylation of nonstructural protein 5.Journal of virology · 2025Article
- An evolutionarily unique viral RdRP suggests a common dual-function feature of the priming element.Science advances · 2025Article
- Structural dynamics of the dengue virus non-structural 5 (NS5) interactions with promoter stem-loop A (SLA).Npj viruses · 2025Article
- The Flavivirus Non-Structural Protein 5 (NS5): Structure, Functions, and Targeting for Development of Vaccines and Therapeutics.Vaccines · 2024Review
- A jingmenvirus RNA-dependent RNA polymerase structurally resembles the flavivirus counterpart but with different features at the initiation phase.Nucleic acids research · 2024Article
- A conformational selection mechanism of flavivirus NS5 for species-specific STAT2 inhibition.Communications biology · 2024Article
- LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities.PLoS pathogens · 2023Article
- Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells.Scientific reports · 2023Article
- The 8-bromobaicalein inhibited the replication of dengue, and Zika viruses and targeted the dengue polymerase.Scientific reports · 2023Article
- Structural basis of transition from initiation to elongation in de novo viral RNA-dependent RNA polymerases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Identification of new inhibitors of NS5 from dengue virus using saturation transfer difference (STD-NMR) and molecular docking studies.RSC advances · 2022Article
- Inhibition of Viral RNA-Dependent RNA Polymerases by Nucleoside Inhibitors: An Illustration of the Unity and Diversity of Mechanisms.International journal of molecular sciences · 2022Review
- Virtual Screening of Drug-Like Compounds as Potential Inhibitors of the Dengue Virus NS5 Protein.Frontiers in chemistry · 2022Article
- Mechanisms of Viral Degradation of Cellular Signal Transducer and Activator of Transcription 2.International journal of molecular sciences · 2022Review
- An induced-fit de novo initiation mechanism suggested by a pestivirus RNA-dependent RNA polymerase.Nucleic acids research · 2021Article
- Characteristics of Classical Swine Fever Virus Variants Derived from Live Attenuated GPEViruses · 2021Article
- Article
- Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The flaviviruses pose serious threats to human health. Being a natural fusion of a methyltransferase (MTase) and an RNA-dependent RNA polymerase (RdRP), NS5 is the most conserved flavivirus protein and an important antiviral target. Previously reported NS5 structures represented by those from the Japanese encephalitis virus (JEV) and Dengue virus serotype 3 (DENV3) exhibit two apparently different global conformations, defining two sets of intra-molecular MTase-RdRP interactions. However, whether these NS5 conformations are conserved in flaviviruses and their specific functions remain elusive. Here we report two forms of DENV serotype 2 (DENV2) NS5 crystal structures representing two conformational states with defined analogies to the JEV-mode and DENV3-mode conformations, respectively, demonstrating the conservation of both conformation modes and providing clues for how different conformational states may be interconnected. Data from in vitro polymerase assays further demonstrate that perturbing the JEV-mode but not the DENV3-mode intra-molecular interactions inhibits catalysis only at initiation, while the cell-based virological analysis suggests that both modes of interactions are important for virus proliferation. Our work highlights the role of MTase as a unique intra-molecular initiation factor specifically only through the JEV-mode conformation, providing an example of conformation-based crosstalk between naturally fused protein functional modules.
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