SARS-CoV-2 S assembly into virions facilitated by host ERM proteins

• 成果类型: Article
• 署名作者: Wang, Jiaming; Tai, Wanbo; Wang, Zhaoyang; Dai, Wenxin; Yang, Mingrui; Guo, Jiajian; He, Pengfei; Nan, Yanan; Li, Tianyu; Zhou, Shuqi; Cui, Dongxiao; Li, Yiqun; Ma, Cuiyan; Zhang, Yue; Li, Dongdong; Zhu, Zhengdan; Chu, Kexin; Wang, Dongdong; Yang, Songhui; Zhuang, Xinyu; Tian, Mingyao; Huang, Mingkang; Zhang, Xianwen; Cheng, Gong; Ma, Wenfu
• 署名单位: Beijing University of Chinese Medicine; Tsinghua University; Shenzhen Bay Laboratory; Shenzhen Center for Disease Control & Prevention (SZCDC); Chinese Academy of Agricultural Sciences
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2504517123
• 发表日期: 2026-02-03
• 页码: e2504517123
• 关键词: sars-cov-2; spike; ERM proteins; viral assembly; structural biology; structural basis; binding; EZRIN; phosphorylation; cytoskeleton; adhesion; MOESIN; cd44; TRAFFICKING; RECOGNITION

摘要

The host cell cytoskeleton plays a critical role in the SARS-CoV-2 life cycle, though the underlying mechanisms remain poorly understood. This study investigates the interaction between the SARS-CoV-2 spike (S) protein and the cytoskeleton-associated ezrin-radixin-moesin (ERM) proteins through biochemical and structural characterization. A previously unidentified ERM-binding motif on the SARS-CoV-2 S protein is identified, revealing that S-ERM interactions are specifically conserved among highly pathogenic coronaviruses, including SARS-CoV, MERS-CoV, and SARS-CoV-2. Functionally, these interactions facilitate S packaging into virions by directing it to assembly sites, utilizing ERM's affinity for negatively curved membranes, akin to its role in cell surface protrusions. Silencing ERM expression significantly reduces SARS-CoV-2 titer, highlighting its essential role in viral propagation. Additionally, leveraging the established role of COPI-mediated trafficking in S localization, a compound is developed to disrupt S-COPI binding, promoting S secretion to the cell surface and effectively reducing viral titers. Our findings revealed a critical host-pathogen interaction that drives S incorporation into virions and identified ERM proteins as key facilitators of coronavirus assembly. Furthermore, our study suggests an antiviral strategy by targeting the S-COPI trafficking pathway. These insights advanced our understanding of coronavirus-host interactions and provided a potential therapeutic approach against SARS-CoV-2 and other highly pathogenic coronaviruses.