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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.
Li, Shun; Li, Xiaobo; Liang, Haowei; Yu, Kuike; Zhai, Jingbo; Xue, Mengzhou; Luo, Zhuojing; Zheng, Chunfu; Zhang, Hao.
Afiliação
  • Li S; Department of Spine Surgery, People's Hospital of Longhua, Affiliated Hospital of Southern Medical University, Shenzhen, China.
  • Li X; Department of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, China.
  • Liang H; Institute of Medical Research, Northwestern Polytechnical University, Xi'an, China.
  • Yu K; Department of Respiratory, Chengdu Seventh People's Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, Sichuan, China.
  • Zhai J; Department of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, China.
  • Xue M; Department of Spine Surgery, People's Hospital of Longhua, Affiliated Hospital of Southern Medical University, Shenzhen, China.
  • Luo Z; Key Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region, Medical College, Inner Mongolia Minzu University, Tongliao, China.
  • Zheng C; Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • Zhang H; Institute of Medical Research, Northwestern Polytechnical University, Xi'an, China.
J Med Virol ; 95(11): e29200, 2023 11.
Article em En | MEDLINE | ID: mdl-37916857
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: SARS-CoV-2 / COVID-19 Limite: Humans Idioma: En Revista: J Med Virol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: SARS-CoV-2 / COVID-19 Limite: Humans Idioma: En Revista: J Med Virol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China