ArticleNucleic acids research2014
RNA-dependent RNA polymerase of Japanese encephalitis virus binds the initiator nucleotide GTP to form a mechanistically important pre-initiation state.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Targeting the catalytic ATP-binding site of Japanese Encephalitis Virus RNA-dependent RNA polymerase using integrated structure-based drug discovery.Folia microbiologica · 2026Article
- Antiviral and neuroprotective activity of diallyl disulfide in Japanese encephalitis virus-challenged SH-SY5Y cells: a post-treatment approach for greater specificity.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Crystallographic Fragment Screening of the Dengue Virus Polymerase Reveals Multiple Binding Sites for the Development of Non-nucleoside Antiflavivirals.Journal of medicinal chemistry · 2025Article
- Identification of Benzothiophene-Derived Inhibitors of Flaviviruses by Targeting RNA-Dependent RNA Polymerase.Viruses · 2025Article
- Binding of Nucleotide Inhibitors to the NS5 RdRp of the ZIKA Virus in the Replication Initiation State.Current medicinal chemistry · 2025Article
- Aryl benzoyl hydrazide derivatives as potent inhibitors of the NS2B-NS3 protease and RNA-dependent RNA polymerase of the zika virus.In silico pharmacology · 2025Article
- Japanese encephalitis virus NS5 protein interacts with nucleolin to enhance the virus replication.Journal of virology · 2024Article
- Japanese encephlu emergence in Australia: the potential population at risk.Annals of medicine and surgery (2012) · 2024Review
- Marine Brown Algae-Derived Compounds as Potential Inhibitors of Japanese Encephalitis Virus RNA-Dependent RNA Polymerase.Marine drugs · 2024Article
- Galidesivir Triphosphate Promotes Stalling of Dengue-2 Virus Polymerase Immediately Prior to Incorporation.ACS infectious diseases · 2023Article
- Discovery of Small Molecules fromLife (Basel, Switzerland) · 2022Article
- Antiviral drug research for Japanese encephalitis: an updated review.Pharmacological reports : PR · 2022Review
- RdRp (RNA-dependent RNA polymerase): A key target providing anti-virals for the management of various viral diseases.Journal of molecular structure · 2022Review
- Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica.Scientific reports · 2021Article
- A novel mechanism of enhanced transcription activity and fidelity for influenza A viral RNA-dependent RNA polymerase.Nucleic acids research · 2021Article
- Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity.NPJ vaccines · 2021Article
- Snapshots of a Non-Canonical RdRP in Action.Viruses · 2021Article
- Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase.Journal of pharmaceutical analysis · 2020Article
- Prediction of Small Molecule Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus-2 RNA-dependent RNA Polymerase.ACS omega · 2020Article
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3 authors.
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Abstract
Flaviviral RNA-dependent RNA polymerases (RdRps) initiate replication of the single-stranded RNA genome in the absence of a primer. The template sequence 5'-CU-3' at the 3'-end of the flaviviral genome is highly conserved. Surprisingly, flaviviral RdRps require high concentrations of the second incoming nucleotide GTP to catalyze de novo template-dependent RNA synthesis. We show that GTP stimulates de novo RNA synthesis by RdRp from Japanese encephalitis virus (jRdRp) also. Crystal structures of jRdRp complexed with GTP and ATP provide a basis for specific recognition of GTP. Comparison of the jRdRpGTP structure with other viral RdRp-GTP structures shows that GTP binds jRdRp in a novel conformation. Apo-jRdRp structure suggests that the conserved motif F of jRdRp occupies multiple conformations in absence of GTP. Motif F becomes ordered on GTP binding and occludes the nucleotide triphosphate entry tunnel. Mutational analysis of key residues that interact with GTP evinces that the jRdRpGTP structure represents a novel pre-initiation state. Also, binding studies show that GTP binding reduces affinity of RdRp for RNA, but the presence of the catalytic Mn(2+) ion abolishes this inhibition. Collectively, these observations suggest that the observed pre-initiation state may serve as a checkpoint to prevent erroneous template-independent RNA synthesis by jRdRp during initiation.
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