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  3. An antibody-based proximity labeling map reveals mechanisms of SARS-CoV-2 inhibition of antiviral immunity

An antibody-based proximity labeling map reveals mechanisms of SARS-CoV-2 inhibition of antiviral immunity

  • Cell Chem Biol. 2022 Jan 20;29(1):5-18.e6. doi: 10.1016/j.chembiol.2021.10.008.
Yuehui Zhang 1,  Limin Shang 1,  Jing Zhang 2,  Yuchen Liu 1,  Chaozhi Jin 1,  Yanan Zhao 1,  Xiaobo Lei 3,  Wenjing Wang 3,  Xia Xiao 3,  Xiuyuan Zhang 1,  Yujiao Liu 4,  Linlin Liu 5,  Meng-Wei Zhuang 2,  Qingkun Mi 1,  Chunyan Tian 1,  Jianwei Wang 6,  Fuchu He 7,  Pei-Hui Wang 8,  Jian Wang 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
  • 2 Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • 3 NHC Key Laboratory of System Biology of Pathogens and Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
  • 4 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China; College of Life Science, Hebei University, Baoding 071002, China.
  • 5 Shandong University Key Laboratory of Immunology, Weifang Medical University, Weifang 261053, China.
  • 6 NHC Key Laboratory of System Biology of Pathogens and Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. Electronic address: wangjw28@163.com.
  • 7 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address: hefc@bmi.ac.cn.
  • 8 Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China. Electronic address: pei-hui.wang@sdu.edu.cn.
  • 9 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address: wangjian@bmi.ac.cn.
PMID: 34672954 DOI: 10.1016/j.chembiol.2021.10.008
Abstract

The global epidemic caused by the coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in the Infection of over 200 million people. To extend the knowledge of interactions between SARS-CoV-2 and humans, we systematically investigate the interactome of 29 Viral Proteins in human cells by using an antibody-based TurboID assay. In total, 1,388 high-confidence human proximal proteins with biotinylated sites are identified. Notably, we find that SARS-CoV-2 manipulates the Antiviral and immune responses. We validate that the membrane protein ITGB1 associates angiotensin-converting Enzyme 2 (ACE2) to mediate SARS-CoV-2 entry. Moreover, we reveal that SARS-CoV-2 Proteins inhibit activation of the interferon pathway through the mitochondrial protein mitochondrial antiviral-signaling protein (MAVS) and the methyltransferase SET domain containing 2, histone lysine methyltransferase (SETD2). We propose 111 potential drugs for the clinical treatment of coronavirus disease 2019 (COVID-19) and identify three compounds that significantly inhibit the replication of SARS-CoV-2. The proximity labeling map of SARS-CoV-2 and humans provides a resource for elucidating the mechanisms of viral Infection and developing drugs for COVID-19 treatment.

Keywords

COVID-19; SARS-CoV-2; TurboID; interactome; proximity labeling.

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