Evidence map›Paper›PMID 33504779›Full record

ArticleNature communications2021

Cryo-EM structures of the SARS-CoV-2 endoribonuclease Nsp15 reveal insight into nuclease specificity and dynamics.

Monica C Pillon, Meredith N Frazier, Lucas B Dillard, Jason G Williams, Seda Kocaman, Juno M Krahn, Lalith Perera, Cassandra K Hayne, Jacob Gordon, Zachary D Stewart and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
8.9field-weighted citation impact, top 1% of its field
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

80 citing papers in PubMed, 136 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Nanocarrier-based immunotherapy for viral diseases.International journal of pharmaceutics: X · 2025
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. SARS-CoV-2 nsp15 enhances viral virulence by subverting host antiviral defenses.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  15. Functional implications of hexameric dynamics in SARS-CoV-2 Nsp15.Protein science : a publication of the Protein Society · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 1 institution in 3 countries.

Monica C Pillon *Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA. monica.pillon@nih.gov.ORCID 0000-0001-8571-6873
Meredith N Frazier *Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
Lucas B Dillard *Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
Jason G WilliamsEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
Seda KocamanSignal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
Juno M KrahnGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
Lalith PereraGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.ORCID 0000-0003-0823-1631
Cassandra K HayneSignal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.ORCID 0000-0002-2485-5949
Jacob GordonSignal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.ORCID 0000-0001-7199-7416
Zachary D StewartSignal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
Mack SobhanySignal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
Leesa J DeterdingEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
Allen L HsuGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.ORCID 0000-0003-2065-3802
Venkata P DandeyGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
Mario J BorgniaGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.ORCID 0000-0001-9159-1413
Robin E StanleySignal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA. robin.stanley@nih.gov.ORCID 0000-0002-2106-3102
National Institutes of Health · US

Funding

Structure and Function of RNA Processing MachinesZIAES103247 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI STANLEY, ROBIN · 2015 to 2025
$22.9M
Protein Microcharacterization ZICES102488 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILLIAMS, JASON · 2009 to 2025
$19.2M
NIEHS Cryo-EM Core FacilityZICES103326 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BORGNIA, MARIO · 2017 to 2025
$17.0M
Macromolecular ModelingZICES043010 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI COPELAND, WILLIAM · 2012 to 2025
$5.7M
Structural and Functional Characterization of the SARS-CoV-2 Endoribonuclease Nsp15ZIAES103340 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI STANLEY, ROBIN · 2020 to 2025
$3.6M
Mass Spectrometry CharacterizationZICES103206 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DETERDING, LEESA · 2018 to 2021
$2.8M
MACROMOLECULAR MODELING AND CARCINOGENESISZ01ES043010 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DARDEN, THOMAS A · 1986 to 2008
$1.2M
Protein MicrocharacterizationZ01ES102488 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILLIAMS, JASON · 2008 to 2008
$564k
Intramural NIH HHS Z01 ES043010Intramural NIH HHS Z01 ES102488Intramural NIH HHS ZIA ES103247Intramural NIH HHS ZIC ES102488Intramural NIH HHS ZIC ES103206Intramural NIH HHS ZIC ES103326
6 · The paper itself

Abstract

Nsp15, a uridine specific endoribonuclease conserved across coronaviruses, processes viral RNA to evade detection by host defense systems. Crystal structures of Nsp15 from different coronaviruses have shown a common hexameric assembly, yet how the enzyme recognizes and processes RNA remains poorly understood. Here we report a series of cryo-EM reconstructions of SARS-CoV-2 Nsp15, in both apo and UTP-bound states. The cryo-EM reconstructions, combined with biochemistry, mass spectrometry, and molecular dynamics, expose molecular details of how critical active site residues recognize uridine and facilitate catalysis of the phosphodiester bond. Mass spectrometry revealed the accumulation of cyclic phosphate cleavage products, while analysis of the apo and UTP-bound datasets revealed conformational dynamics not observed by crystal structures that are likely important to facilitate substrate recognition and regulate nuclease activity. Collectively, these findings advance understanding of how Nsp15 processes viral RNA and provide a structural framework for the development of new therapeutics.

Indexed as

Amino Acid SequenceCatalytic DomainCryoelectron MicroscopyEndoribonucleasesModels, ChemicalModels, MolecularSARS-CoV-2Uridine TriphosphateViral Nonstructural ProteinsEndoribonucleasesnidoviral uridylate-specific endoribonucleaseUridine TriphosphateViral Nonstructural Proteins

Identifiers

PMID33504779
PMCPMC7840905
OpenAlexW3122688266

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.