SNX27 suppresses SARS-CoV-2 infection by inhibiting viral lysosome/late endosome entry

• DOI: 10.1073/pnas.2117576119
• Publication Date: 2022-01-12T22:15:24Z
• Authors: 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 Fu Gao; Jianxun Qi; Guijun Shang
• Keywords: Sorting nexin; Retromer; PDZ domain; Internalization

Significance We here established the interaction between PDZ binding motif (PBM) at C terminal of ACE2 and domain sorting nexin 27 (SNX27) solved crystal structure ACE2-PBM/SNX27-PDZ complex. Together with retromer complex, SNX27 was found to regulate homeostasis cell surface under physiological conditions. When endocytic pathway used during SARS-CoV-2 infection, SNX27-retromer sorts ACE2/SARS-CoV-2 complex early endosome prevents it from entering lysosome/late endosome, inhibiting entry virus. These findings add substantially current understanding important role cytosolic tail invasion SARS-CoV-2, could be as a new therapeutic target for drug development.