Evidence map›Paper›PMID 33723254›Full record

ArticleNature communications2021

SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication.

Yuchen Zhang, Rui Guo, Sharon H Kim, Hardik Shah, Shuting Zhang, Jin Hua Liang, Ying Fang, Matteo Gentili, Colin N O' Leary, Steven J Elledge and 3 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 107 papers.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed
8.5field-weighted citation impact, top 2% 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

107 citing papers in PubMed, 148 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Host metabolic responses to SARS-CoV-2 and influenza viruses: parallels and contrasts.Metabolomics : Official journal of the Metabolomic Society · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. MTHFR allele and one-carbon metabolic profile predict severity of COVID-19.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

47 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

13 authors at 3 institutions in 2 countries.

Yuchen Zhang *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Rui Guo *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sharon H Kim *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Hardik Shah *Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-8408-5686
Shuting ZhangBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jin Hua LiangBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Ying FangDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Matteo GentiliBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-6970-8133
Colin N O' LearyDivision of Genetics, Brigham and Women's Hospital, Department of Genetics, Howard Hughes Medical Institute, Program in Virology, Harvard Medical School, Boston, MA, USA.
Steven J ElledgeDivision of Genetics, Brigham and Women's Hospital, Department of Genetics, Howard Hughes Medical Institute, Program in Virology, Harvard Medical School, Boston, MA, USA.
Deborah T HungBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-4262-0673
Vamsi K MoothaBroad Institute of MIT and Harvard, Cambridge, MA, USA. vamsi_mootha@hms.harvard.edu.
Benjamin E GewurzBroad Institute of MIT and Harvard, Cambridge, MA, USA. bgewurz@bwh.harvard.edu.ORCID 0000-0002-3965-3418
Broad Institute · USBrigham and Women's Hospital · USUniversity of Illinois Urbana-Champaign · US

Funding

Mitochondrial Parts, Pathways, and PathogenesisR35GM122455 · NIGMS · BROAD INSTITUTE, INC. · PI MOOTHA, VAMSI KRISHNA · 2017 to 2021
$4.0M
Epstein-Barr virus LMP1 mediated oncogenicityR01CA228700 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Benjamin Elison Gewurz · 2019 to 2026
$3.3M
Metabolic Network Remodeling in Epstein-Barr Virus LymphomagenesisR01AI137337 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI GEWURZ, BENJAMIN ELISON · 2018 to 2022
$2.2M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA228700NIAID NIH HHS R01 AI137337NIGMS NIH HHS R35 GM122455
6 · The paper itself

Abstract

The recently identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. How this novel beta-coronavirus virus, and coronaviruses more generally, alter cellular metabolism to support massive production of ~30 kB viral genomes and subgenomic viral RNAs remains largely unknown. To gain insights, transcriptional and metabolomic analyses are performed 8 hours after SARS-CoV-2 infection, an early timepoint where the viral lifecycle is completed but prior to overt effects on host cell growth or survival. Here, we show that SARS-CoV-2 remodels host folate and one-carbon metabolism at the post-transcriptional level to support de novo purine synthesis, bypassing viral shutoff of host translation. Intracellular glucose and folate are depleted in SARS-CoV-2-infected cells, and viral replication is exquisitely sensitive to inhibitors of folate and one-carbon metabolism, notably methotrexate. Host metabolism targeted therapy could add to the armamentarium against future coronavirus outbreaks.

Indexed as

Virus ReplicationA549 CellsAnimalsCarbonChlorocebus aethiopsCOVID-19Cytopathogenic Effect, ViralFolic AcidFolic Acid AntagonistsGlucoseHumansMethotrexateRNA, ViralSARS-CoV-2SerineTranscription, GeneticCarbonFolic AcidFolic Acid AntagonistsGlucoseMethotrexateRNA, ViralSerineViral Proteins

Identifiers

PMID33723254
PMCPMC7960988
OpenAlexW3139503800

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.