Open AccessSNX27 suppresses SARS-CoV-2 infection by inhibiting viral lysosome/late endosome entry
Author(s) -
Bo Yang,
Yuanyuan Jia,
Yumin Meng,
Ying Xue,
Kefang Liu,
Yan Li,
Shichao Liu,
Xiaoxiong Li,
Kaige Cui,
Lina Shang,
Tianyou Cheng,
Zhichao Zhang,
Yingxiang Hou,
Xiaozhu Yang,
Hong Yan,
Liqiang Duan,
Zhou Tong,
Changxin Wu,
Zhida Liu,
Shan Gao,
Shu Zhuo,
Weijin Huang,
George F. Gao,
Jianxun Qi,
Guijun Shang
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2117576119
Subject(s) - sorting nexin , retromer , endosome , pdz domain , microbiology and biotechnology , endocytic cycle , lysosome , biology , chemistry , endocytosis , cell , biochemistry , intracellular , enzyme
Significance We here established the interaction between PDZ binding motif (PBM) at the C terminal of ACE2 and PDZ domain of sorting nexin 27 (SNX27) and solved the crystal structure of ACE2-PBM/SNX27-PDZ complex. Together with retromer complex, SNX27 was found to regulate the homeostasis of cell surface ACE2 under physiological conditions. When endocytic pathway was used during SARS-CoV-2 infection, SNX27-retromer sorts ACE2/SARS-CoV-2 complex at early endosome and prevents it from entering lysosome/late endosome, inhibiting the cell entry of the virus. These findings add substantially to the current understanding of the important role of cytosolic tail of ACE2 during the invasion of SARS-CoV-2, and it could be used as a new therapeutic target for drug development.