tetano
Editor, Senior Moderator
J Med Virol
. 2023 Nov;95(11):e29200.
doi: 10.1002/jmv.29200. SARS-CoV-2 ORF7a blocked autophagy flux by intervening in the fusion between autophagosome and lysosome to promote viral infection and pathogenesis
Shun Li[SUP] 1 2 3 [/SUP], Xiaobo Li[SUP] 4 [/SUP], Haowei Liang[SUP] 2 [/SUP], Kuike Yu[SUP] 1 [/SUP], Jingbo Zhai[SUP] 5 [/SUP], Mengzhou Xue[SUP] 6 [/SUP], Zhuojing Luo[SUP] 3 7 [/SUP], Chunfu Zheng[SUP] 8 [/SUP], Hao Zhang[SUP] 1 [/SUP]
Affiliations
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.
Keywords: COVID-19; ORF7a; SARS-CoV-2; autophagy; lysosome.
. 2023 Nov;95(11):e29200.
doi: 10.1002/jmv.29200. SARS-CoV-2 ORF7a blocked autophagy flux by intervening in the fusion between autophagosome and lysosome to promote viral infection and pathogenesis
Shun Li[SUP] 1 2 3 [/SUP], Xiaobo Li[SUP] 4 [/SUP], Haowei Liang[SUP] 2 [/SUP], Kuike Yu[SUP] 1 [/SUP], Jingbo Zhai[SUP] 5 [/SUP], Mengzhou Xue[SUP] 6 [/SUP], Zhuojing Luo[SUP] 3 7 [/SUP], Chunfu Zheng[SUP] 8 [/SUP], Hao Zhang[SUP] 1 [/SUP]
Affiliations
- PMID: 37916857
- DOI: 10.1002/jmv.29200
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.
Keywords: COVID-19; ORF7a; SARS-CoV-2; autophagy; lysosome.