tetano
Editor, Senior Moderator
Nat Commun
. 2021 Mar 15;12(1):1676.
doi: 10.1038/s41467-021-21903-z.
SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication
Yuchen Zhang[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Rui Guo[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Sharon H Kim[SUP] #[/SUP][SUP] 1 5 [/SUP], Hardik Shah[SUP] #[/SUP][SUP] 1 5 [/SUP], Shuting Zhang[SUP] 1 [/SUP], Jin Hua Liang[SUP] 1 2 3 [/SUP], Ying Fang[SUP] 6 [/SUP], Matteo Gentili[SUP] 1 [/SUP], Colin N O' Leary[SUP] 7 [/SUP], Steven J Elledge[SUP] 7 [/SUP], Deborah T Hung[SUP] 1 [/SUP], Vamsi K Mootha[SUP] 8 9 [/SUP], Benjamin E Gewurz[SUP] 10 11 12 [/SUP]
Affiliations
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.
. 2021 Mar 15;12(1):1676.
doi: 10.1038/s41467-021-21903-z.
SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication
Yuchen Zhang[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Rui Guo[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Sharon H Kim[SUP] #[/SUP][SUP] 1 5 [/SUP], Hardik Shah[SUP] #[/SUP][SUP] 1 5 [/SUP], Shuting Zhang[SUP] 1 [/SUP], Jin Hua Liang[SUP] 1 2 3 [/SUP], Ying Fang[SUP] 6 [/SUP], Matteo Gentili[SUP] 1 [/SUP], Colin N O' Leary[SUP] 7 [/SUP], Steven J Elledge[SUP] 7 [/SUP], Deborah T Hung[SUP] 1 [/SUP], Vamsi K Mootha[SUP] 8 9 [/SUP], Benjamin E Gewurz[SUP] 10 11 12 [/SUP]
Affiliations
- PMID: 33723254
- DOI: 10.1038/s41467-021-21903-z
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.