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The global succinylation of SARS-CoV-2-infected host cells reveals drug targets.
Liu, Quan; Wang, Heming; Zhang, He; Sui, Liyan; Li, Letian; Xu, Wang; Du, Shouwen; Hao, Pengfei; Jiang, Yuhang; Chen, Jing; Qu, Xiaoyun; Tian, Mingyao; Zhao, Yinghua; Guo, Xuerui; Wang, Xingye; Song, Wu; Song, Guangqi; Wei, Zhengkai; Hou, Zhijun; Wang, Guoqing; Sun, Minhua; Li, Xiao; Lu, Huijun; Zhuang, Xinyu; Jin, Ningyi; Zhao, Yicheng; Li, Chang; Liao, Ming.
  • Liu Q; Key Laboratory of Livestock Disease Prevention of Guangdong Province, Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences,
  • Wang H; Center for Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory of Human-Animal Zoonotic infectious Diseases, The First Hospital of Jilin University, Changchun, 130021 China.
  • Zhang H; Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122 China.
  • Sui L; School of Life Sciences and Engineering, Foshan University, 528011 Foshan, China.
  • Li L; Department of Gastroenterology, Zhongshan Hospital, Fudan University, 200437 Shanghai, China.
  • Xu W; Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122 China.
  • Du S; Center for Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory of Human-Animal Zoonotic infectious Diseases, The First Hospital of Jilin University, Changchun, 130021 China.
  • Hao P; Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122 China.
  • Jiang Y; Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122 China.
  • Chen J; Department of Infectious Diseases, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, 518020 Shenzhen, China.
  • Qu X; Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122 China.
  • Tian M; Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122 China.
  • Zhao Y; Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122 China.
  • Guo X; Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, 510642 Guangzhou, China.
  • Wang X; Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122 China.
  • Song W; Center for Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory of Human-Animal Zoonotic infectious Diseases, The First Hospital of Jilin University, Changchun, 130021 China.
  • Song G; School of Pharmacy, Jilin University, 130012 Changchun, China.
  • Wei Z; Clinical Medical College, Changchun University of Chinese Medicine, 130117 Changchun, China.
  • Hou Z; Clinical Medical College, Changchun University of Chinese Medicine, 130117 Changchun, China.
  • Wang G; Department of Gastroenterology, Zhongshan Hospital, Fudan University, 200437 Shanghai, China.
  • Sun M; Shanghai Institute of Liver Diseases, 200032 Shanghai, China.
  • Li X; School of Life Sciences and Engineering, Foshan University, 528011 Foshan, China.
  • Lu H; College of Wildlife and Protected Area, Northeast Forestry University, 150040 Harbin, China.
  • Zhuang X; Department of Pathogenbiology, College of Basic Medicine, Jilin University, 130012 Changchun, China.
  • Jin N; Key Laboratory of Livestock Disease Prevention of Guangdong Province, Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences,
  • Zhao Y; Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122 China.
  • Li C; Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122 China.
  • Liao M; Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122 China.
Proc Natl Acad Sci U S A ; 119(30): e2123065119, 2022 07 26.
Article in English | MEDLINE | ID: covidwho-1947760
ABSTRACT
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 posttranslational modification and cellular pathways mediated by SARS-CoV-2, which may become antiviral drug targets against COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Protein Processing, Post-Translational / Host-Pathogen Interactions / Molecular Targeted Therapy / SARS-CoV-2 / COVID-19 / COVID-19 Drug Treatment Topics: Variants Limits: Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Protein Processing, Post-Translational / Host-Pathogen Interactions / Molecular Targeted Therapy / SARS-CoV-2 / COVID-19 / COVID-19 Drug Treatment Topics: Variants Limits: Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2022 Document Type: Article