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SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication #MMPMID33723254
Zhang Y; Guo R; Kim SH; Shah H; Zhang S; Liang JH; Fang Y; Gentili M; Leary CNO; Elledge SJ; Hung DT; Mootha VK; Gewurz BE
Nat Commun 2021[Mar]; 12 (1): 1676 PMID33723254show ga
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.
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Nat+Commun 2021 ; 12 (1): 1676
