SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication.
SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication.
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DOI:
10.1038/s41467-021-21903-z
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发表时间:
2021-03-15
影响因子:
16.6
通讯作者:
Gewurz BE
中科院分区:
文献类型:
--
作者:
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
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. Viruses rely on host metabolism for replication. Here, the authors perform transcriptional and metabolomic analyses at 8 hours after SARS-CoV-2 infection and find that the virus alters host folate and one-carbon metabolism at a post-transcriptional level.
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影响因子:
6.7
作者:
Irigoyen N;Firth AE;Jones JD;Chung BY;Siddell SG;Brierley I
通讯作者:
Brierley I
DOI:
10.1038/nrmicro.2016.81
发表时间:
2016-08
期刊:
Nature reviews. Microbiology
影响因子:
--
作者:
de Wit E;van Doremalen N;Falzarano D;Munster VJ
通讯作者:
Munster VJ
DOI:
10.1073/pnas.0603144103
发表时间:
2006-08-22
影响因子:
11.1
作者:
Kamitani, Wataru;Narayanan, Krishna;Makino, Shinji
通讯作者:
Makino, Shinji
影响因子:
11.4
作者:
García-Cañaveras JC;Lancho O;Ducker GS;Ghergurovich JM;Xu X;da Silva-Diz V;Minuzzo S;Indraccolo S;Kim H;Herranz D;Rabinowitz JD
通讯作者:
Rabinowitz JD
影响因子:
29
作者:
Codo, Ana Campos;Davanzo, Gustavo Gastao;Moraes-Vieira, Pedro M.
通讯作者:
Moraes-Vieira, Pedro M.