Evidence map›Paper›PMID 34083449›Full record

ArticleScience (New York, N.Y.)2021

Fe-S cofactors in the SARS-CoV-2 RNA-dependent RNA polymerase are potential antiviral targets.

Nunziata Maio, Bernard A P Lafont, Debangsu Sil, Yan Li, J Martin Bollinger, Carsten Krebs, Theodore C Pierson, W Marston Linehan, Tracey A Rouault

Open access · hybridAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
5.0field-weighted citation impact, top 3% 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

75 citing papers in PubMed, 122 citations in OpenAlex.

  1. Review
  2. Article
  3. Insights into SARS-CoV-2 replication controlActa pharmaceutica Sinica. B · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Crystallise, poise, capture: a multimodal platform for correlated structural and spectroscopic characterisation of redox enzymes.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Nunziata MaioEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-6225-6058
Bernard A P LafontSARS-CoV-2 Virology Core, Laboratory of Viral Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0003-2140-6205
Debangsu SilDepartment of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.ORCID 0000-0002-0718-3925
Yan LiProteomics Core Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0003-3820-5960
J Martin BollingerDepartment of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.ORCID 0000-0003-0751-8585
Carsten KrebsDepartment of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.ORCID 0000-0002-3302-7053
Theodore C PiersonLaboratory of Viral Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-3795-4348
W Marston LinehanUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.ORCID 0000-0001-7983-3109
Tracey A RouaultEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. rouault@mail.nih.gov.ORCID 0000-0003-0062-0245
National Institutes of Health · USPennsylvania State University · USNational Cancer Institute · USNational Institute of Allergy and Infectious Diseases · US

Funding

Molecular Therapeutics of Kidney Cancer: VHL Gene and Fumarate Hydratase GeneZIABC011038 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LINEHAN, WILLIAM MARSTON · 2009 to 2025
$29.8M
Mammalian iron-sulfur cluster biogenesisZIAHD008814 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI ROUAULT, TRACEY A. · 2009 to 2025
$17.8M
Mechanisms of Mononuclear non-Heme-Iron EnzymesR35GM127079 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI CARSTEN KREBS · 2018 to 2026
$3.8M
NIGMS NIH HHS R35 GM127079
6 · The paper itself

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19, uses an RNA-dependent RNA polymerase (RdRp) for the replication of its genome and the transcription of its genes. We found that the catalytic subunit of the RdRp, nsp12, ligates two iron-sulfur metal cofactors in sites that were modeled as zinc centers in the available cryo-electron microscopy structures of the RdRp complex. These metal binding sites are essential for replication and for interaction with the viral helicase. Oxidation of the clusters by the stable nitroxide TEMPOL caused their disassembly, potently inhibited the RdRp, and blocked SARS-CoV-2 replication in cell culture. These iron-sulfur clusters thus serve as cofactors for the SARS-CoV-2 RdRp and are targets for therapy of COVID-19.

Indexed as

Amino Acid MotifsAnimalsAntiviral AgentsBinding SitesCatalytic DomainChlorocebus aethiopsCoenzymesCoronavirus RNA-Dependent RNA PolymeraseCyclic N-OxidesEnzyme InhibitorsIronProtein DomainsRNA HelicasesSARS-CoV-2Spin LabelsSulfurAntiviral AgentsCoenzymesCoronavirus RNA-Dependent RNA PolymeraseCyclic N-OxidesEnzyme InhibitorsIronNSP12 protein, SARS-CoV-2RNA HelicasesSpin LabelsSulfurtempolViral Nonstructural ProteinsZinc

Identifiers

PMID34083449
PMCPMC8892629
OpenAlexW3164001450

What OpenQuestion 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 OpenQuestion graph.