Targeting CTP Synthetase 1 to Restore Interferon Induction and Impede Nucleotide Synthesis in SARS-CoV-2 Infection

de novo CTP synthesis while shutting down IFN induction. De novo synthesis of small-molecule inhibitors of CTPS1 enabled CTP depletion and IFN induction in SARS-CoV-2 infection, thus impeding SARS-CoV-2 replication. Our work uncovers a strategy that a viral pathogen couples immune evasion to metabol...

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Bibliographic Details
Published in:bioRxiv 2021-02
Main Authors: Rao, Youliang, Ting-Yu, Wang, Chao, Qin, Espinosa, Bianca, Liu, Qizhi, Ekanayake, Arunika, Zhao, Jun, Ali Can Savas, Zhang, Shu, Zarinfar, Mehrnaz, Liu, Yongzhen, Zhu, Wenjie, Graham, Nicholas, Jiang, Taijiao, Zhang, Chao, Feng, Pinghui
Format: Article
Language:English
Subjects:
Antiviral agents
Interferon
Metabolic activation
Metabolic rate
Replication
Severe acute respiratory syndrome coronavirus 2
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Summary:de novo CTP synthesis while shutting down IFN induction. De novo synthesis of small-molecule inhibitors of CTPS1 enabled CTP depletion and IFN induction in SARS-CoV-2 infection, thus impeding SARS-CoV-2 replication. Our work uncovers a strategy that a viral pathogen couples immune evasion to metabolic activation to fuel viral replication. Inhibition of the cellular CTPS1 offers an attractive means for developing antiviral therapy that would be resistant to SARS-CoV-2 mutation. Competing Interest Statement The authors have declared no competing interest. Footnotes * ↵6 Lead Contact.
DOI:10.1101/2021.02.05.429959