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, Deborah T. Hung, Vamsi K. Mootha () and Benjamin E. Gewurz ()
Additional contact information
Yuchen Zhang: Broad Institute of MIT and Harvard
Rui Guo: Broad Institute of MIT and Harvard
Sharon H. Kim: Broad Institute of MIT and Harvard
Hardik Shah: Broad Institute of MIT and Harvard
Shuting Zhang: Broad Institute of MIT and Harvard
Jin Hua Liang: Broad Institute of MIT and Harvard
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
Benjamin E. Gewurz: Broad Institute of MIT and Harvard

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-21903-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21903-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-21903-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().