tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2026 Feb 3;123(5):e2504517123.
doi: 10.1073/pnas.2504517123. Epub 2026 Jan 30.
SARS-CoV-2 S assembly into virions facilitated by host ERM proteins
Jiaming Wang[SUP] #[/SUP][SUP] 1 [/SUP], Wanbo Tai[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Zhaoyang Wang[SUP] 2 3 4 [/SUP], Wenxin Dai[SUP] 1 [/SUP], Mingrui Yang[SUP] 1 [/SUP], Jiajian Guo[SUP] 1 [/SUP], Pengfei He[SUP] 1 [/SUP], Yanan Nan[SUP] 1 [/SUP], Tianyu Li[SUP] 1 [/SUP], Shuqi Zhou[SUP] 1 [/SUP], Dongxiao Cui[SUP] 1 [/SUP], Yiqun Li[SUP] 1 [/SUP], Cuiyan Ma[SUP] 1 [/SUP], Yue Zhang[SUP] 1 [/SUP], Dongdong Li[SUP] 5 [/SUP], Zhengdan Zhu[SUP] 5 [/SUP], Kexin Chu[SUP] 5 [/SUP], Dongdong Wang[SUP] 5 [/SUP], Songhui Yang[SUP] 6 [/SUP], Xinyu Zhuang[SUP] 6 [/SUP], Mingyao Tian[SUP] 6 [/SUP], Mingkang Huang[SUP] 3 [/SUP], Xianwen Zhang[SUP] 3 [/SUP], Gong Cheng[SUP] 2 3 4 7 [/SUP], Wenfu Ma[SUP] 1 [/SUP]
Affiliations
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.
Keywords: ERM proteins; SARS-CoV-2; spike; structural biology; viral assembly.
. 2026 Feb 3;123(5):e2504517123.
doi: 10.1073/pnas.2504517123. Epub 2026 Jan 30.
SARS-CoV-2 S assembly into virions facilitated by host ERM proteins
Jiaming Wang[SUP] #[/SUP][SUP] 1 [/SUP], Wanbo Tai[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Zhaoyang Wang[SUP] 2 3 4 [/SUP], Wenxin Dai[SUP] 1 [/SUP], Mingrui Yang[SUP] 1 [/SUP], Jiajian Guo[SUP] 1 [/SUP], Pengfei He[SUP] 1 [/SUP], Yanan Nan[SUP] 1 [/SUP], Tianyu Li[SUP] 1 [/SUP], Shuqi Zhou[SUP] 1 [/SUP], Dongxiao Cui[SUP] 1 [/SUP], Yiqun Li[SUP] 1 [/SUP], Cuiyan Ma[SUP] 1 [/SUP], Yue Zhang[SUP] 1 [/SUP], Dongdong Li[SUP] 5 [/SUP], Zhengdan Zhu[SUP] 5 [/SUP], Kexin Chu[SUP] 5 [/SUP], Dongdong Wang[SUP] 5 [/SUP], Songhui Yang[SUP] 6 [/SUP], Xinyu Zhuang[SUP] 6 [/SUP], Mingyao Tian[SUP] 6 [/SUP], Mingkang Huang[SUP] 3 [/SUP], Xianwen Zhang[SUP] 3 [/SUP], Gong Cheng[SUP] 2 3 4 7 [/SUP], Wenfu Ma[SUP] 1 [/SUP]
Affiliations
- PMID: 41615754
- DOI: 10.1073/pnas.2504517123
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.
Keywords: ERM proteins; SARS-CoV-2; spike; structural biology; viral assembly.