莫诺拉韦在体外/体内抗H1N1流行性感冒病毒感染特点的研究  

Characteristics of molnupiravir in anti-H1N1 influenza virus infection in vitro and in vivo

作　　者：冯茜莉 王进千 杨宣叶 胡欣妍 丁玉林[3] 马晓霞[1,2] FENG Xili;WANG Jinqian;YANG Xuanye;HU Xinyan;DING Yulin;MA Xiaoxia(Key Laboratory of Bioengineering and Biotechnology of State Ethnic Affairs Commission,Biomedical Research Center,Northwest Minzu University,Lanzhou 730030,China;College of Life Science and Engineering,Northwest Minzu University,Lanzhou 730010,China;Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Diseases,Ministry of Agriculture and Rural Affairs,College of Veterinary Medicine,Inner Mongolia Agricultural University,Hohhot 010018,China)

机构地区：[1]西北民族大学生物医学研究中心生物工程与技术国家民委重点实验室,甘肃兰州730030 [2]西北民族大学生命科学与工程学院,甘肃兰州730010 [3]内蒙古农业大学兽医学院农业农村部动物疾病临床诊疗技术重点实验室,内蒙古呼和浩特010018

出　　处：《中国感染控制杂志》2025年第4期478-485,共8页Chinese Journal of Infection Control

基　　金：甘肃省自然科学基金项目(20JR5RA505)。

摘　　要：目的分析莫诺拉韦在体内和体外对流行性感冒(流感)病毒的抗病毒效果。方法检测莫诺拉韦对流感病毒H1N1 PR8毒株在体外和体内的抗病毒能力。以人源非小细胞肺癌细胞系(A549细胞)作为PR8感染的体外模型,采用实时荧光定量聚合酶链反应(qRT-PCR)、免疫印迹试验(WB)、噬斑的方法,分析莫诺拉韦体外对病毒复制、蛋白合成及病毒颗粒形成方面的抗病毒效果。以PR8滴鼻感染C57BL/6雌性小鼠为体内感染模型,分别从病毒载量、病理变化及免疫组化方面,对对照组、给药组、接毒组和接毒-给药组进行检测,以评估莫诺拉韦的抗病毒能力。结果体外试验结果显示,莫诺拉韦对流感病毒的复制、蛋白合成及病毒颗粒形成没有明显抑制作用(均P>0.05)。小鼠体内试验结果显示,与单纯感染H1N1小鼠相比,接受莫诺拉韦治疗的小鼠肺组织病毒载量明显下降,病理变化程度较轻,免疫组化检测显示核蛋白(NP)抗原信号明显减弱,干扰素(IFN)-α、白细胞介素(IL)-4和IL-6在肺中的表达水平较低(均P<0.01)。结论作为具有抗病毒活性的前体物,莫诺拉韦无法在体外培养的肺源细胞中发挥抗病毒活力,但可以在宿主体内转化为活性形式,显著降低H1N1流感病毒在肺增殖的能力,进而减轻病毒对肺组织的损伤。Objective To analyze the antiviral effect of molnupiravir against influenza virus in vitro and in vivo.Methods The antiviral ability of molnupiravir against influenza virus strain H1N1 PR8 was detected in vitro and in vivo.Human non-small cell lung cancer cell line(A549 cells)was used as an in vitro model of PR8 infection.The antiviral effects of molnupiravir on virus replication,protein synthesis,and viral particle formation were analyzed using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR),Western blot(WB)assay,and plaque assay.PR8 nose-dripping infected C57BL/6 female mice were used as an in vivo infection model.The antiviral ability of molnupiravir was evaluated by detecting viral load,pathological changes,and immunohistochemistry in the control group,administration group,inoculation group,and inoculation-administration group.Results In vitro test results showed that molnupiravir had no significant inhibitory effect on influenza virus replication,protein synthesis,and virus particle formation(all P>0.05).In vivo test results showed that compared with mice infected with H1N1 alone,the viral load in the lung tissue of mice treated with molnupiravir declined significantly,and the extent of pathological changes was milder.Immunohistochemical detection showed a significant weakening in nuclear protein(NP)antigen signal,and the expression levels of interferon(IFN)-α,interleukin(IL)-4,and IL-6 in the lungs were lower(all P<0.01).Conclusion As a precursor with antiviral activity,molnupiravir can not exert antiviral activity in lung-derived cells cultured in vitro,but can be transformed into an active form in the host,which significantly decreases the ability of H1N1 influenza virus to proliferate in the lungs and thereby alleviates the da-mage of virus to lung tissue.

关 键 词：莫诺拉韦 流行性感冒 抗病毒 感染模型 病理变化 H1N1 

分 类 号：R181.32[医药卫生—流行病学] R511.7[医药卫生—公共卫生与预防医学]