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SARS-CoV-2 ORF7a blocked autophagy flux by intervening in the fusion between autophagosome and lysosome to promote viral infection and pathogenesis

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机构: [1]Department of Spine Surgery, People's Hospital of Longhua, Affiliated Hospital of Southern Medical University, Shenzhen, China. [2]Department of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, China. [3]Institute of Medical Research, Northwestern Polytechnical University, Xi'an, China. [4]Department of Respiratory, Chengdu Seventh People's Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, Sichuan, China. [5]Key Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region, Medical College, Inner Mongolia Minzu University, Tongliao, China. [6]Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. [7]Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China. [8]Department of Microbiology, Immunology & Infection Diseases, University of Calgary, Calgary, Canada.
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关键词: autophagy COVID‐19 lysosome ORF7a SARS‐CoV‐2

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The coronavirus disease 2019 (COVID-19) continues to pose a major threat to public health worldwide. Although many studies have clarified the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection process, the underlying mechanisms of viral invasion and immune evasion were still unclear. This study focused on SARS-CoV-2 ORF7a (open reading frame-7a), one of the essential open reading frames (ORFs) in infection and pathogenesis. First, by analyzing its physical and chemical characteristics, SARS-CoV-2 ORF7a is an unstable hydrophobic transmembrane protein. Then, the ORF7a transmembrane domain three-dimensional crystal structure model was predicted and verified. SARS-CoV-2 ORF7a localized in the endoplasmic reticulum and participated in the autophagy-lysosome pathway via interacting with p62. In addition, we elucidated the underlying molecular mechanisms by which ORF7a intercepted autophagic flux, promoted double membrane vesicle formation, and evaded host autophagy-lysosome degradation and antiviral innate immunity. This study demonstrated that ORF7a could be a therapeutic target, and Glecaprevir may be a potential drug against SARS-CoV-2 by targeting ORF7a. A comprehensive understanding of ORF7a's functions may contribute to developing novel therapies and clinical drugs against COVID-19.© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.

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大类 | 3 区 医学
小类 | 3 区 病毒学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 病毒学
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Q1 VIROLOGY
最新[2023]版:
Q1 VIROLOGY

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第一作者机构: [1]Department of Spine Surgery, People's Hospital of Longhua, Affiliated Hospital of Southern Medical University, Shenzhen, China. [2]Department of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, China. [3]Institute of Medical Research, Northwestern Polytechnical University, Xi'an, China.
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通讯机构: [3]Institute of Medical Research, Northwestern Polytechnical University, Xi'an, China. [7]Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
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