We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
SARS‐CoV‐2 ORF7a blocked autophagy flux by intervening in the fusion between autophagosome and lysosome to promote viral infection and pathogenesis.
- Authors
Li, Shun; Li, Xiaobo; Liang, Haowei; Yu, Kuike; Zhai, Jingbo; Xue, Mengzhou; Luo, Zhuojing; Zheng, Chunfu; Zhang, Hao
- Abstract
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.
- Subjects
SARS-CoV-2; VIRUS diseases; COVID-19; TRANSMEMBRANE domains
- Publication
Journal of Medical Virology, 2023, Vol 95, Issue 11, p1
- ISSN
0146-6615
- Publication type
Article
- DOI
10.1002/jmv.29200