SARS-CoV-2 S assembly into virions facilitated by host ERM proteins
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (25)
Jiaming Wang
School of Life Sciences, Beijing University of Chinese Medicine
Wanbo Tai
New Cornerstone Science Laboratory, Tsinghua University-Peking University, Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University
Zhaoyang Wang
Wenxin Dai
School of Life Sciences, Beijing University of Chinese Medicine
Mingrui Yang
School of Life Sciences, Beijing University of Chinese Medicine
Jiajian Guo
School of Life Sciences, Beijing University of Chinese Medicine
Pengfei He
School of Life Sciences, Beijing University of Chinese Medicine
Yanan Nan
School of Life Sciences, Beijing University of Chinese Medicine
Tianyu Li
Shuqi Zhou
Tsinghua University , , ,
Dongxiao Cui
School of Life Sciences, Beijing University of Chinese Medicine
Yiqun Li
School of Life Sciences, Beijing University of Chinese Medicine
Cuiyan Ma
School of Life Sciences, Beijing University of Chinese Medicine
Yue Zhang
Dongdong Li
Key Laboratory for Ultrafine Materials of Ministry of Education, Shanghai Engineering Research Center of Hierarchical Nanomaterials, School of Materials Science and Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China
Zhengdan Zhu
DP Technology
Kexin Chu
DP Technology
Dongdong Wang
Songhui Yang
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control
Xinyu Zhuang
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control
Mingyao Tian
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control
Mingkang Huang
Institute of Infectious Diseases, Shenzhen Bay Laboratory
Xianwen Zhang
Gong Cheng
Wenfu Ma
School of Life Sciences, Beijing University of Chinese Medicine