• 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.
• Broad Institute of MIT and Harvard, Cambridge, MA, USA.
• Nat Commun. 2021 Mar 15; 12 (1): 1676.

AbstractThe 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.

34 keywords...

hide…