广谱抗病毒药物吐根碱抑制HCoV-OC43的转录组分析  

Transcriptomic Analysis of the Broad-Spectrum Antiviral Drug Emetine Inhibiting HCoV-OC43

作　　者：李涵 张高倩 吴长城 张钟贤 牛军伟[2] 霍恕婷 叶飞[2] 邓瑶[2] 黄保英[2] 赵莉[2] 沈晓玲 谭文杰 LI Han;ZHANG Gaoqian;WU Changcheng;ZHANG Zhongxian;NIU Junwei;HUO Shuting;YE Fei;DENG Yao;HUANG Baoying;ZHAO Li;SHEN Xiaoling;TAN Wenjie(School of Public Health,Baotou Medical College,Baotou 014040,China;National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases(NITFID),NHC Key Laboratory of Biosafety,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 100052,China;Department of Microbiology,Basic Medical College,Inner Mongolia Medical University,Hohhot 010010,China)

机构地区：[1]包头医学院公共卫生学院,包头014040 [2]传染病溯源预警与智能决策全国重点实验室,中国疾病预防控制中心病毒病预防控制所,国家卫生健康委员会生物安全重点实验室,北京102206 [3]内蒙古医科大学基础医学院微生物教研室,呼和浩特010010

出　　处：《病毒学报》2024年第3期458-468,共11页Chinese Journal of Virology

基　　金：国家重点研发计划(项目号:2023YFC3041500),题目:奥密克戎变异规律分析与防控研究;国家重点研发计划(项目号:2021YFA1201003),题目:抗病毒纳米药物的体内外功能评价;国家自然科学基金(项目号:U21A20384),题目:基于PROTAC技术靶向降解SARS-CoV-2 Mpro蛋白的新型广谱抗冠状病毒药物的研发。

摘　　要：本研究旨在探索吐根碱对人冠状病毒OC43(Human coronavirus OC43, HCoV-OC43)的作用时相和抗病毒机制。首先,在MRC-5细胞上建立了HCoV-OC43病毒的体外感染复制动力学曲线,测定了药物的EC_(50)和CC_(50)。结果表明吐根碱能够在感染早期有效地抑制HCoV-OC43病毒在MRC-5细胞中的复制。通过转录组分析,发现HCoV-OC43感染和吐根碱处理均导致宿主基因表达的紊乱,并且两者共同激活了抗病毒通路。吐根碱可能通过激活OASL、Mx1和IFIT2等抗病毒基因来增强宿主对病毒的抵抗能力。此外,吐根碱还可能通过抑制TMEM41B表达而进一步影响病毒复制过程。这些研究结果为深入探究吐根碱作为抗冠状病毒药物的机制和潜在靶点提供了重要线索。We aimed to investigate the timing of the antiviral effects of emetine and its mechanism of action on the human coronavirus OC43(HCoV-OC43).First,we established an extracellular infection-and-replication curve for HCoV-OC43 in MRC-5 cells and determined the half-maximal effective concentration(EC_(50))and concentration required to reduce cell viability by 50%(CC_(50))of emetine.Emetine inhibited HCoV-OC43 replication in MRC-5 cells effectively during the early stages of infection.Transcriptome analysis revealed that HCoV-OC43 infection and emetine treatment led to a disorder in host-gene expression while activating antiviral pathways.Emetine could enhance host resistance to viruses by activating antiviral genes such as OASL,Mx1,and IFIT2.Also,by inhibiting TMEM41B expression,emetine could further affect HCoV-OC43 replication.These findings hold important implications for exploring the mechanism and potential targets of emetine as an anti-coronavirus drug.

关 键 词：吐根碱 HCoV-OC43 抗病毒作用 转录组学 基因表达紊乱 

分 类 号：R373.1[医药卫生—病原生物学]