The global succinylation of SARS-CoV-2-infected host cells reveals drug targets

文献类型： 外文期刊

第一作者： Liu, Quan

作者： Liu, Quan;Sun, Minhua;Liao, Ming;Liu, Quan;Sui, Liyan;Zhao, Yinghua;Zhao, Yicheng;Liu, Quan;Zhang, He;Li, Letian;Xu, Wang;Hao, Pengfei;Jiang, Yuhang;Chen, Jing;Tian, Mingyao;Li, Xiao;Lu, Huijun;Zhuang, Xinyu;Jin, Ningyi;Li, Chang;Liu, Quan;Wei, Zhengkai;Wang, Heming;Song, Guangqi;Du, Shouwen;Qu, Xiaoyun;Liao, Ming;Guo, Xuerui;Wang, Xingye;Song, Wu;Song, Guangqi;Hou, Zhijun;Wang, Guoqing;Liao, Ming

作者机构：

关键词： SARS-CoV-2; succinylproteomics; antiviral; SIRT5; NSP14

期刊名称：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA （ 影响因子：11.1； 五年影响因子：12.0 ）

ISSN： 0027-8424

年卷期： 2022 年 119 卷 30 期

页码：

收录情况： SCI

摘要： SARS-CoV-2, the causative agent of the COVID-19 pandemic, undergoes continuous evolution, highlighting an urgent need for development of novel antiviral therapies. Here we show a quantitative mass spectrometry-based succinylproteomics analysis of SARS-CoV-2 infection in Caco-2 cells, revealing dramatic reshape of succinylation on host and viral proteins. SARS-CoV-2 infection promotes succinylation of several key enzymes in the TCA, leading to inhibition of cellular metabolic pathways. We demonstrated that host protein succinylation is regulated by viral nonstructural protein (NSP14) through interaction with sirtuin 5 (SIRT5); overexpressed SIRT5 can effectively inhibit virus replication. We found succinylation inhibitors possess significant antiviral effects. We also found that SARS-CoV-2 nucleocapsid and membrane proteins underwent succinylation modification, which was conserved in SARS-CoV-2 and its variants. Collectively, our results uncover a regulatory mechanism of host protein post-translational modification and cellular pathways mediated by SARS-CoV-2, which may become antiviral drug targets against COVID-19.

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