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

Author

Listed:
  • Yuchen Zhang

    (Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital
    Harvard Medical School
    State Key Laboratory of Oncology in South China)

  • Rui Guo

    (Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Sharon H. Kim

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Hardik Shah

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Shuting Zhang

    (Broad Institute of MIT and Harvard)

  • Jin Hua Liang

    (Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Ying Fang

    (University of Illinois at Urbana-Champaign)

  • Matteo Gentili

    (Broad Institute of MIT and Harvard)

  • Colin N. O’ Leary

    (Harvard Medical School)

  • Steven J. Elledge

    (Harvard Medical School)

  • Deborah T. Hung

    (Broad Institute of MIT and Harvard)

  • Vamsi K. Mootha

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Benjamin E. Gewurz

    (Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital
    Harvard Medical School)

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.

Suggested Citation

  • 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 & Deborah T. Hung & Vamsi K. Mootha & Benjamin, 2021. "SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21903-z
    DOI: 10.1038/s41467-021-21903-z
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    Cited by:

    1. Daniel Strebinger & Chris J. Frangieh & Mirco J. Friedrich & Guilhem Faure & Rhiannon K. Macrae & Feng Zhang, 2023. "Cell type-specific delivery by modular envelope design," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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