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.
Original language | English (US) |
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Article number | 1676 |
Journal | Nature communications |
Volume | 12 |
Issue number | 1 |
Early online date | Mar 15 2021 |
DOIs | |
State | Published - Mar 15 2021 |
Keywords
- Coronavirus
- COVID-19
- severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
- Novel coronavirus
- 2019-nCoV
- Pandemic
ASJC Scopus subject areas
- General Physics and Astronomy
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology