文献类型： 外文期刊

作者： Liu, Quan ¹ ; Wang, Heming ⁵ ; Zhang, He ³ ; Sui, Liyan ² ; Li, Letian ³ ; Xu, Wang ³ ; Du, Shouwen ⁶ ; Hao, Pengfei ³ ; Jiang, Yuhang ³ ; Chen, Jing ³ ; Qu, Xiaoyun ⁷ ; Tian, Mingyao ³ ; Zhao, Yinghua ² ; Guo, Xuerui ⁸ ; Wang, Xingye ⁹ ; Song, Wu ⁹ ; Song, Guangqi ⁵ ; Wei, Zhengkai ⁴ ; Hou, Zhijun ¹¹ ; Wang, Guoqing ¹² ; Sun, Minhua ¹ ; Li, Xiao ³ ; Lu, Huijun ³ ; Zhuang, Xinyu ³ ; Jin, Ningyi ³ ; Zhao, Yicheng ² ; Li, Chang ³ ; Liao, Ming ¹ ;

作者机构： 1.Guangdong Acad Agr Sci, Key Lab Livestock Dis Prevent Guangdong Prov, Sci Observat & Expt Stn Vet Drugs & Diagnost Tech, Minist Agr & Rural Affairs,Inst Anim Hlth, Guangzhou 510610, Peoples R China

2.First Hosp Jilin Univ, Key Lab Organ Regenerat & Transplantat, State Key Lab Human Anim Zoonot Infect Dis, Minist Educ,Ctr Infect Dis & Pathogen Biol, Changchun 130021, Peoples R China

3.Chinese Acad Agr Sci, Chinese Acad Med Sci, Changchun Vet Res Inst, Res Unit Key Technol Prevent & Control Virus Zoon, Changchun 130122, Peoples R China

4.Foshan Univ, Sch Life Sci & Engn, Foshan 528011, Peoples R China

5.Fudan Univ, Zhongshan Hosp, Dept Gastroenterol, Shanghai 200437, Peoples R China

6.Jinan Univ, Dept Infect Dis, Clin Med Coll 2, Shenzhen Peoples Hosp, Shenzhen 518020, Peoples R China

7.South China Agr Univ, Minist Agr & Rural Affairs, Key Lab Zoonosis, Guangzhou 510642, Peoples R China

8.Jilin Univ, Sch Pharm, Changchun 130012, Peoples R China

9.Changchun Univ Chinese Med, Clin Med Coll, Changchun 130117, Peoples R China

10.Shanghai Inst Liver Dis, Shanghai 200032, Peoples R China

11.Northeast Forestry Univ, Coll Wildlife & Protected Area, Harbin 150040, Peoples R China

12.Jilin Univ, Coll Basic Med, Dept Pathogenbiol, Changchun 130012, Peoples R China

13.Guangdong Lab Lingnan Modern Agr, Maoming Branch, Maoming 525000, Peoples R China

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.