Evidence map›Paper›PMID 40299982›Full record

ArticlePLoS biology2025

Variant mutation G215C in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation.

Hannah C Kubinski, Hannah W Despres, Bryan A Johnson, Madaline M Schmidt, Sara A Jaffrani, Allyson H Turner, Conor D Fanuele, Margaret G Mills, Kumari G Lokugamage, Caroline M Dumas and 14 more

Abstract read
In one paragraph

Article in PLoS biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Evolution of a fuzzy ribonucleoprotein complex in viral assembly.bioRxiv : the preprint server for biology · 2025
    Article
  10. Review
  11. Article
  12. Article
  13. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Hannah C KubinskiDepartment of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, Vermont, United States of America.
Hannah W DespresDepartment of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, Vermont, United States of America.
Bryan A JohnsonDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
Madaline M SchmidtDepartment of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, Vermont, United States of America.
Sara A JaffraniDepartment of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, Vermont, United States of America.
Allyson H TurnerDepartment of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, Vermont, United States of America.
Conor D FanueleDepartment of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, Vermont, United States of America.
Margaret G MillsVirology Division, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, United States of America.
Kumari G LokugamageDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
Caroline M DumasDepartment of Biology, University of Vermont, Burlington, Vermont, United States of America.
David J ShirleyFaraday, Inc. Data Science Department, Burlington, Vermont, United States of America.
Leah K EstesDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
Andrew PekoszW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
Jessica W CrothersDepartment of Pathology and Laboratory Medicine, Robert Larner, MD College of Medicine, University of Vermont, Burlington, Vermont, United States of America.
Pavitra RoychoudhuryVirology Division, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, United States of America.
Alexander L GreningerVirology Division, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, United States of America.
Keith R JeromeVirology Division, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, United States of America.
Bruno Martorelli Di GenovaDepartment of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, Vermont, United States of America.
David H WalkerDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
Bryan A BallifDepartment of Biology, University of Vermont, Burlington, Vermont, United States of America.
Mark S LadinskyDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, United States of America.
Pamela J BjorkmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, United States of America.
Vineet D MenacheryDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
Emily A BruceDepartment of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, Vermont, United States of America.ORCID https://orcid.org/0000-0001-8391-370X

Funding

Vermont INBRE Administrative Supplement 2024 AWD 118P20GM103449 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI CHRISTOPHER S FRANCKLYN · 2012 to 2026
$58.4M
Using Dengue Controlled Human Infection Model to Identify Adaptive Immune Correlates of ProtectionP20GM125498 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Kristen Pierce · 2018 to 2026
$24.9M
The longevity and nature of the anti-SARS-CoV-2 cellular and humoral immune responsesP01AI165075 · NIAID · ROCKEFELLER UNIVERSITY · PI BIENIASZ, PAUL D., BJORKMAN, PAMELA J · 2022 to 2023
$10.7M
Identifying host and viral correlates for coronavirus pathogenesisR01AI153602 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI JOHNSON, BRYAN A · 2020 to 2023
$2.0M
NIAID NIH HHS P01 AI165075NIAID NIH HHS R01 AI153602NIGMS NIH HHS P20 GM103449NIGMS NIH HHS P20 GM125498
6 · The paper itself

Abstract

The evolution of SARS-CoV-2 variants and their respective phenotypes represents an important set of tools to understand basic coronavirus biology as well as the public health implications of individual mutations in variants of concern. While mutations outside of spike are not well studied, the entire viral genome is undergoing evolutionary selection, with several variants containing mutations in the central disordered linker region of the nucleocapsid (N) protein. Here, we identify a mutation (G215C), characteristic of the Delta variant, that introduces a novel cysteine into this linker domain, which results in the formation of a more stable N-N dimer. Using reverse genetics, we determined that this cysteine residue is necessary and sufficient for stable dimer formation in a WA1 SARS-CoV-2 background, where it results in significantly increased viral growth both in vitro and in vivo. Mechanistically, we show that the N:G215C mutant has more encapsidation as measured by increased RNA binding to N, N incorporation into virions, and electron microscopy showing that individual virions are larger, with elongated morphologies.

Indexed as

Coronavirus Nucleocapsid ProteinsCOVID-19NucleocapsidSARS-CoV-2Viral Genome PackagingAnimalsChlorocebus aethiopsGenome, ViralHumansMutationPhosphoproteinsVero CellsVirionVirus AssemblyCoronavirus Nucleocapsid Proteinsnucleocapsid phosphoprotein, SARS-CoV-2Phosphoproteins

Identifiers

PMID40299982
PMCPMC12040272

What OpenQuestion holds

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Registered trials

None linked

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.