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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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
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Language:English
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Antiviral agents
Interferon
Metabolic activation
Metabolic rate
Replication
Severe acute respiratory syndrome coronavirus 2
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container_title bioRxiv
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creator 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
description 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_str_mv 10.1101/2021.02.05.429959
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source Coronavirus Research Database
subjects Antiviral agents
Interferon
Metabolic activation
Metabolic rate
Replication
Severe acute respiratory syndrome coronavirus 2
title Targeting CTP Synthetase 1 to Restore Interferon Induction and Impede Nucleotide Synthesis in SARS-CoV-2 Infection
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