ArticleNucleic acids research2022
Crystal structures of alphavirus nonstructural protein 4 (nsP4) reveal an intrinsically dynamic RNA-dependent RNA polymerase fold.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- The life cycle of the alphaviruses: From an antiviral perspective.Antiviral research · 2023Pooled it
- Research progress on the role of host factors in Chikungunya virus infection and intervention strategies.Virulence · 2026Review
- RNAViruses · 2026Review
- Recent progress in anti-Chikungunya virus drug discovery: Focus on the viral life cycle and direct-acting antivirals.Virologica Sinica · 2026Review
- Alphavirus nsP3 as a multifunctional orchestrator of virus-host interplay.Journal of virology · 2026Review
- Identification and characterization of novel chikungunya virus polymerase inhibitors.Journal of virology · 2026Article
- Positive-Strand RNA Viral RdRps: From Structure Conservation and Activity Assay to Drug Development.Molecules (Basel, Switzerland) · 2026Review
- Venezuelan equine encephalitis virus: novel live-attenuated vaccines for inducing complete protective immunity.Npj viruses · 2026Review
- Discovery of BPR2-D2 compound in inhibiting Chikungunya viral RNA synthesis by replicon systems.Biomedical journal · 2026Article
- A fold switch regulates conformation of an alphavirus RNA-dependent RNA polymerase.Nucleic acids research · 2026Article
- Chikungunya in 2025: Comprehensive Insights into Virology, Diagnostics, Vaccines, and Antiviral Therapies.Viruses · 2026Review
- Rewiring of host cell signaling in chikungunya virus infection: a mechanism for pathogenesis and therapeutic approaches.Archives of microbiology · 2026Review
- Trans-complementation of chikungunya virus replicase mutants reveals alphavirus replication complexity and supports antiviral tool development.PLoS pathogens · 2025Article
- CC-90009, a Cereblon E3 Ligase Modulator, Exhibits Antiviral Efficacy Against JEV In Vitro and In Vivo via Targeted Degradation of GSPT1 and Viral NS5 Protein.Pharmaceutics · 2025Article
- A fold switch regulates conformation of an alphavirus virus RNA-dependent RNA polymerase.bioRxiv : the preprint server for biology · 2025Article
- Effectiveness of 3-amino-2-thiocyanato-α, β-unsaturated carbonyl compounds against chikungunya virus.Future medicinal chemistry · 2025Article
- Alphavirus nsP2: A Multifunctional Regulator of Viral Replication and Promising Target for Anti-Alphavirus Therapies.Reviews in medical virology · 2025Review
- YBX1 is required for assembly of viral replication complexes of chikungunya virus and replication of multiple alphaviruses.Journal of virology · 2025Article
- Global Transmission and Evolution of Chikungunya Virus: Origins, Adaptive Mutations, and Intercontinental Spread of the Three Genotypes.Transboundary and emerging diseases · 2025Article
- Mutations in chikungunya virus nsP4 decrease viral fitness and sensitivity to the broad-spectrum antiviral 4'-Fluorouridine.PLoS pathogens · 2025Article
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Alphaviruses such as Ross River virus (RRV), chikungunya virus (CHIKV), Sindbis virus (SINV), and Venezuelan equine encephalitis virus (VEEV) are mosquito-borne pathogens that can cause arthritis or encephalitis diseases. Nonstructural protein 4 (nsP4) of alphaviruses possesses RNA-dependent RNA polymerase (RdRp) activity essential for viral RNA replication. No 3D structure has been available for nsP4 of any alphaviruses despite its importance for understanding alphaviral RNA replication and for the design of antiviral drugs. Here, we report crystal structures of the RdRp domain of nsP4 from both RRV and SINV determined at resolutions of 2.6 Å and 1.9 Å. The structure of the alphavirus RdRp domain appears most closely related to RdRps from pestiviruses, noroviruses, and picornaviruses. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) and nuclear magnetic resonance (NMR) methods showed that in solution, nsP4 is highly dynamic with an intrinsically disordered N-terminal domain. Both full-length nsP4 and the RdRp domain were capable to catalyze RNA polymerization. Structure-guided mutagenesis using a trans-replicase system identified nsP4 regions critical for viral RNA replication.
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