ArticleNucleic acids research2020
A nucleobase-binding pocket in a viral RNA-dependent RNA polymerase contributes to elongation complex stability.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Pyridin-3-carbohydrazide strongly impairs Mayaro and Chikungunya virus replication in vitro.Archives of virology · 2026Article
- Diversity and distinctive characteristics of the global RNA virome in urban and peri-urban environments.Nature communications · 2026Article
- Discovery of non-nucleoside inhibitors of the enterovirus D68 3D polymerase through crystallographic fragment and high-throughput biochemical screening.bioRxiv : the preprint server for biology · 2026Article
- Heterodimerization of PRRSV replicase membrane proteins nsp2 and nsp3 regulates their cytoplasmic tail binding to viral RdRp domain for sgRNA synthesis.Journal of virology · 2026Article
- Mutation in enterovirus 71 nonstructural protein 3A increases genome replication fidelity and exhibits attenuated virulence in mice.Journal of virology · 2025Article
- Hijacking the Host Cell for Replication: Pro-Viral Host Factors Involved in EVA71 Infection.International journal of molecular sciences · 2025Review
- Deep mutation, insertion and deletion scanning across the Enterovirus A proteome reveals constraints shaping viral evolution.Nature microbiology · 2025Article
- EV71 5'UTR interacts with 3D protein affecting replication through the AKT-mTOR pathway.Virology journal · 2024Article
- RPflex: A Coarse-Grained Network Model for RNA Pocket Flexibility Study.International journal of molecular sciences · 2023Article
- Molecular architecture of the Chikungunya virus replication complex.Science advances · 2022Article
- On the Recognition of Natural Substrate CTP and Endogenous Inhibitor ddhCTP of SARS-CoV-2 RNA-Dependent RNA Polymerase: A Molecular Dynamics Study.Journal of chemical information and modeling · 2022Article
- Revisiting Viral RNA-Dependent RNA Polymerases: Insights from Recent Structural Studies.Viruses · 2022Review
- Crystal structures of alphavirus nonstructural protein 4 (nsP4) reveal an intrinsically dynamic RNA-dependent RNA polymerase fold.Nucleic acids research · 2022Article
- Induced intra- and intermolecular template switching as a therapeutic mechanism against RNA viruses.Molecular cell · 2021Article
- Potential effect of Maxing Shigan decoction against coronavirus disease 2019 (COVID-19) revealed by network pharmacology and experimental verification.Journal of ethnopharmacology · 2021Article
- Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis.Nature communications · 2020Article
- An Extended Primer Grip of Picornavirus Polymerase Facilitates Sexual RNA Replication Mechanisms.Journal of virology · 2020Article
- Stringent control of the RNA-dependent RNA polymerase translocation revealed by multiple intermediate structures.Nature communications · 2020Article
- Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase.bioRxiv : the preprint server for biology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The enterovirus 71 (EV71) 3Dpol is an RNA-dependent RNA polymerase (RdRP) that plays the central role in the viral genome replication, and is an important target in antiviral studies. Here, we report a crystal structure of EV71 3Dpol elongation complex (EC) at 1.8 Å resolution. The structure reveals that the 5'-end guanosine of the downstream RNA template interacts with a fingers domain pocket, with the base sandwiched by H44 and R277 side chains through hydrophobic stacking interactions, and these interactions are still maintained after one in-crystal translocation event induced by nucleotide incorporation, implying that the pocket could regulate the functional properties of the polymerase by interacting with RNA. When mutated, residue R277 showed an impact on virus proliferation in virological studies with residue H44 having a synergistic effect. In vitro biochemical data further suggest that mutations at these two sites affect RNA binding, EC stability, but not polymerase catalytic rate (kcat) and apparent NTP affinity (KM,NTP). We propose that, although rarely captured by crystallography, similar surface pocket interaction with nucleobase may commonly exist in nucleic acid motor enzymes to facilitate their processivity. Potential applications in antiviral drug and vaccine development are also discussed.
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