After coronavirus infection, the host endomembrane system is remodeled to form double‑membrane vesicles (DMVs) that serve as platforms for viral RNA synthesis. The endoplasmic reticulum has been considered the primary membrane source for DMV formation, but whether the Golgi apparatus and its vesicle transport system are involved has remained incompletely understood.
Recently, a collaborative team led by Deyin Guo from Guangzhou National Laboratory, Panpan Hou from Guangzhou Medical University, and Chun‑Mei Li from Sun Yat‑sen University published a study in hLife entitled “Golgi‑derived COPI vesicles fuel the biogenesis of coronavirus replication organelles.” The study reveals that coronaviruses hijack the host GBF1‑ARF1‑COPI vesicle transport pathway to utilize Golgi‑derived membranes for promoting DMV formation.
“This provides a new perspective for understanding how coronaviruses reprogram the host membrane trafficking system,” said Associate Professor Chun‑Mei Li, the corresponding author. “Viruses do not rely on a single membrane source; they may systematically hijack the cellular membrane trafficking network. We found that coronaviruses recruit Golgi‑derived membranes to their replication organelles through COPI vesicles, thereby identifying a conserved host pathway commonly exploited by multiple coronaviruses. This provides a theoretical basis for the development of host‑directed antiviral drugs.”
To identify the membrane source, the team used APEX2 proximity‑labeling proteomics—a technique that labels proteins adjacent to the viral protein nsp3—and identified the GBF1‑ARF1‑COPI pathway as a top candidate. Through systematic validation using siRNA knockdown, CRISPR/Cas9 gene editing, and the specific GBF1 inhibitor Golgicide A (GCA), they found that disruption of this pathway severely impaired DMV formation and viral RNA synthesis. Transmission electron microscopy showed that DMVs became smaller and fewer in number when GBF1 or COPI components were depleted. Sucrose density gradient centrifugation and cell imaging further confirmed that Golgi membranes were recruited to DMV formation sites in a COPI‑dependent manner. Importantly, this mechanism was conserved across multiple coronaviruses, including SARS‑CoV‑2, mouse hepatitis virus (MHV), and the common‑cold coronavirus HCoV‑229E.
In C57BL/6J mice infected with MHV, GCA treatment significantly reduced viral RNA loads and viral titers in lung and liver tissues, while also alleviating tissue pathological damage. These results suggest that pharmacological targeting of GBF1 may be a viable strategy against coronavirus infection. The GBF1‑ARF1‑COPI axis represents a promising host‑directed broad‑spectrum antiviral intervention target. Future research will explore whether this pathway can be exploited for therapeutic development against other positive‑strand RNA viruses that also depend on host membrane remodeling.
This work was conducted by researchers at Sun Yat‑sen University, Guangzhou Medical University, and Guangzhou National Laboratory. This study was supported by National Natural Science Foundation of China (grant numbers 82394461 and 32470160), Guangdong Basic and Applied Basic Research Foundation (grant number 2025A1515010591), Major Project of Guangzhou National Laboratory (grant numbers GZNL2024A01008 and GZNL2023A01008), the China Postdoctoral Science Foundation (grant number 2025M772755), and the Open Research Project of the Key Laboratory of Viral Pathogenesis & Infection Prevention and Control of the Ministry of Education (grant number 2025VPPC‑R10).
About Author:
Dr. Chun-Mei Li is an Associate Professor and Doctoral Supervisor at the School of Medicine, Sun Yat-sen University. She obtained her Master's and Ph.D. degrees in Microbiology from the Department of Biosciences, University of Helsinki, in 2003 and 2007, respectively. After completing her Ph.D. in 2007, she pursued postdoctoral training at the Haartman Institute, Faculty of Medicine, University of Helsinki, and later moved to the Institute of Biotechnology at the same university in 2010. During her tenure at the University of Helsinki, her research focused on the immunopathogenic mechanisms of infectious diseases, particularly bacterial infections. Upon returning to China, her research interests have shifted to the mechanisms of viral infection, replication, and antiviral immune regulation. She also employs electron microscopy and 3D reconstruction techniques to investigate the dynamic interactions between the endoplasmic reticulum, biomacromolecules, and viruses. For more information, please visit her research homepage at https://szmed.sysu.edu.cn/zh-hans/teacher/1261.
D OI Link:
https://doi.org/10.1016/j.hlife.2026.06.004
hLife
Golgi-derived COPI vesicles fuel the biogenesis of coronavirus replication organelles
17-Jul-2026