SNX10 enhances HCoV-OC43 infection by facilitating viral entry and inhibiting virus-triggered autophagy

Haobin Li; Huiyi Guo; Binhao Rong; Haowei Li; Wenjiao Wu; Chan Yang; Shuwen Liu

doi:10.1016/j.virs.2025.07.005

October 2025

Haobin Li, Huiyi Guo, Binhao Rong, Haowei Li, Wenjiao Wu, Chan Yang and Shuwen Liu. SNX10 enhances HCoV-OC43 infection by facilitating viral entry and inhibiting virus-triggered autophagy[J]. Virologica Sinica, 2025, 40(5): 755-768. doi: 10.1016/j.virs.2025.07.005

Citation: Haobin Li, Huiyi Guo, Binhao Rong, Haowei Li, Wenjiao Wu, Chan Yang, Shuwen Liu. SNX10 enhances HCoV-OC43 infection by facilitating viral entry and inhibiting virus-triggered autophagy .VIROLOGICA SINICA, 2025, 40(5) : 755-768. http://dx.doi.org/10.1016/j.virs.2025.07.005

SNX10通过促进病毒进入和抑制病毒诱导的自噬正向调控来增强HCoV-OC43冠状病毒的感染

李豪斌 ^a ,
郭慧仪 ^a ,
容彬豪 ^a ,
李浩威 ^a ,
武文娇 ^b ,
杨婵 ^a,c ,
刘叔文 ^a,c,d,e,,

a 南方医科大学药学院粤港澳新药筛选联合实验室, 广东省新药筛选重点实验室;
b. 暨南大学附属广东省第二人民医院药学部;
c. 南方医科大学 "华南传染病防治"教育部重点实验室, 教育部炎症与免疫相关疾病医学基础研究创新中心;
d. 南方医科大学深圳坪山医院药学部药物代谢研究与评价国家重点实验室;
e. 南方医科大学器官衰竭研究国家重点实验室, 广东省肾脏病研究所

通讯作者： 刘叔文, liusw@smu.edu.cn
收稿日期： 2025-03-22
录用日期： 2025-07-07

摘要

包括新型冠状病毒（COVID-19）在内的冠状病毒疫情继续对全球公共卫生构成重大威胁。宿主蛋白参与病毒生命周期的多个阶段，因此靶向宿主蛋白的治疗方针有望成为有希望的治疗策略。本研究确定分选蛋白10（SNX10）是促进人类冠状病毒OC43（HCoV-OC43）复制的宿主因子，强调了其作为新型抗病毒靶点的潜力。基因敲除SNX10能显著抑制HCoV-OC43在体内和体外的复制。免疫沉淀-质谱（IP-MS）分析发现，适配蛋白复合物2亚基μ1（AP2M1）是SNX10的直接互助蛋白。SNX10可促进AP2M1的磷酸化，从而增强网格蛋白介导的病毒内吞。随后的病毒结合和病毒内化试验显示，SNX10基因敲除能显著抑制病毒的进入。重组表达外源性SNX10能够恢复病毒进入宿主细胞的效率，证实SNX10在病毒内化过程中具有不可或缺的关键作用。与此同时，SNX10被确定为通过调节pH促进内体酸化的关键因素，进一步促进病毒基因组的释放。值得注意的是，在感染过程中SNX10缺失会激活细胞的自噬反应提高自噬通量，通过消除病原体来维持细胞内环境稳态，并且SNX10还通过溶酶体降解途径发挥自主抗病毒作用。综上所述，SNX10是病毒生命周期的关键调节因子，并强调了它作为一种多方面抗病毒候选药物的治疗潜力，具备抑制病毒内化、病毒基因组释放和维持宿主-病原体平衡的关键能力。
- 分选蛋白10（SNX10）
- , HCoV-OC43感染
- , 宿主因子
- , 内体酸化
- , 自噬流

SNX10 enhances HCoV-OC43 infection by facilitating viral entry and inhibiting virus-triggered autophagy

Haobin Li ^a ,
Huiyi Guo ^a ,
Binhao Rong ^a ,
Haowei Li ^a ,
Wenjiao Wu ^b ,
Chan Yang ^a,c ,
Shuwen Liu ^a,c,d,e,,

a. Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China;
b. Department of Pharmacy, Jinan University Affiliated Guangdong Second Provincial General Hospital, Guangzhou, 510317, China;
c. MOE Key Laboratory of Infectious Diseases Research in South China, MOE Innovation Center for Medical Basic Research on Inflammation and Immune Related Diseases, Southern Medical University, Guangzhou, 510515, China;
d. NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Department of Pharmacy, Pingshan Hospital, Southern Medical University, Shenzhen, 518100, China;
e. State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, 510515, China

Corresponding author: Shuwen Liu, liusw@smu.edu.cn
Received Date: 22 March 2025
Accepted Date: 07 July 2025

Abstract

The ongoing coronavirus epidemic, including the novel coronavirus (SARS-CoV-2), continues to pose a significant threat to global public health. Host targets address multiple stages of the viral life cycle and provide diverse opportunities for therapeutic interventions. This study identified sorting nexin 10 (SNX10) as a facilitator of replication of human coronavirus OC43 (HCoV-OC43), underscoring its potential as a novel antiviral target. The knockout of SNX10 significantly suppressed HCoV-OC43 replication both in vivo and in vitro. Immunoprecipitation-mass spectrometry (‌IP-MS) analysis identified the adaptor protein complex 2 subunit μ1 (AP2M1) as a direct interactor of SNX10. Specifically, SNX10 facilitates phosphorylation of the AP2M1, thereby enhancing clathrin-mediated viral endocytosis. Furthermore, subsequent binding and internalization assays revealed that SNX10 knockout significantly inhibits viral entry into host cells. Conversely, the reconstitution of SNX10 fully restored viral entry, thereby confirming the critical and indispensable role of SNX10 in pathogen internalization. Simultaneously, SNX10 was identified as a key factor that promotes endosomal acidification by modulating pH levels, which in turn facilitated the release of the viral genome. Notably, the ablation of SNX10 was found to trigger autophagy activation during infection, thereby maintaining intracellular homeostasis. Additionally, it exerted autonomous antiviral effects through lysosomal degradation pathways. Collectively, these findings demonstrate SNX10 serves as a pivotal regulator of the viral life cycle and underscore its therapeutic potential as a multi-faceted antiviral candidate target capable of simultaneously inhibiting viral internalization, viral genomic release, and host-pathogen equilibrium.
- Sorting nexin 10 (SNX10)
- , Coronavirus infection
- , Host factor
- , Endosomal acidification
- , Autophagic flux

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