ArticleProceedings of the National Academy of Sciences of the United States of America2012
Structural and functional insights into alphavirus polyprotein processing and pathogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.
- The life cycle of the alphaviruses: From an antiviral perspective.Antiviral research · 2023Pooled it
- Expression and Purification of nsP2 Protease of Chikungunya Virus.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Development of a novel hybrid alphavirus-Nipah virus pseudovirion for rapid quantification of vaccine-induced neutralization antibodies.Emerging microbes & infections · 2026Article
- Alphavirus nsP3 as a multifunctional orchestrator of virus-host interplay.Journal of virology · 2026Review
- Alphavirus replicase and regulatory RNA elements in host interactions and viral vector engineering.Journal of virology · 2026Review
- Engineering drug-responsive replication machinery for precise control of self-amplifying RNA.Nature biomedical engineering · 2026Article
- A conserved in-frame stop codon acts as a multipotent defense mechanism in alphaviruses.Science advances · 2026Article
- Molecular mechanisms of protease precursor autoprocessing of RNA viruses: a comprehensive review.Virology journal · 2026Review
- Biocompatible ligand balancing in transition metal coordination enables benign in-cell protein arylation.Nature chemistry · 2026Article
- A High-Throughput Antiviral Assay Based on a Sindbis Virus-GFP for the Discovery of Inhibitors of Alphavirus Replication.Viruses · 2026Article
- Antagonism of RNA silencing in the yellow fever mosquito,Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Novel computational pipeline to identify target sites for broad spectrum antiviral drugs.Antiviral research · 2026Article
- The Sindbis virus nsP3 opal codon protects viral RNA and fitness by maintaining replication spherule integrity.bioRxiv : the preprint server for biology · 2025Article
- The kinetics of nsp7-11 polyprotein processing and impact on complexation with nsp16 among human coronaviruses.Nature communications · 2025Article
- Engineering gene expression dynamics via self-amplifying RNA with drug-responsive non-structural proteins.bioRxiv : the preprint server for biology · 2025Article
- The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Unveiling the structural and functional implications of uncharacterized NSPs and variations in the molecular toolkit across arteriviruses.NAR genomics and bioinformatics · 2025Article
- A conserved opal termination codon optimizes a temperature-dependent trade-off between protein production and processing in alphaviruses.Science advances · 2025Article
- Proximity interactome of alphavirus replicase component nsP3 includes proviral host factors eIF4G and AHNAK.PLoS pathogens · 2025Article
- Alphavirus nsP2: A Multifunctional Regulator of Viral Replication and Promising Target for Anti-Alphavirus Therapies.Reviews in medical virology · 2025Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Alphaviruses, a group of positive-sense RNA viruses, are globally distributed arboviruses capable of causing rash, arthritis, encephalitis, and death in humans. The viral replication machinery consists of four nonstructural proteins (nsP1-4) produced as a single polyprotein. Processing of the polyprotein occurs in a highly regulated manner, with cleavage at the P2/3 junction influencing RNA template use during genome replication. Here, we report the structure of P23 in a precleavage form. The proteins form an extensive interface and nsP3 creates a ring structure that encircles nsP2. The P2/3 cleavage site is located at the base of a narrow cleft and is not readily accessible, suggesting a highly regulated cleavage. The nsP2 protease active site is over 40 Å away from the P2/3 cleavage site, supporting a trans cleavage mechanism. nsP3 contains a previously uncharacterized protein fold with a zinc-coordination site. Known mutations in nsP2 that result in formation of noncytopathic viruses or a temperature sensitive phenotype cluster at the nsP2/nsP3 interface. Structure-based mutations in nsP3 opposite the location of the nsP2 noncytopathic mutations prevent efficient cleavage of P23, affect RNA infectivity, and alter viral RNA production levels, highlighting the importance of the nsP2/nsP3 interaction in pathogenesis. A potential RNA-binding surface, spanning both nsP2 and nsP3, is proposed based on the location of ion-binding sites and adaptive mutations. These results offer unexpected insights into viral protein processing and pathogenesis that may be applicable to other polyprotein-encoding viruses such as HIV, hepatitis C virus (HCV), and Dengue virus.
Indexed as
Identifiers
What OpenQuestion holds
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.