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Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway

作     者:Chaoxiang Lv Yuanguo Li Tiecheng Wang Qiqi Zhang Jing Qi Mingwei Sima Entao Li Tian Qin Zhuangzhuang Shi Fangxu Li Xuefeng Wang Weiyang Sun Na Feng Songtao Yang Xianzhu Xia Ningyi Jin Yifa Zhou Yuwei Gao Chaoxiang Lv;Yuanguo Li;Tiecheng Wang;Qiqi Zhang;Jing Qi;Mingwei Sima;Entao Li;Tian Qin;Zhuangzhuang Shi;Fangxu Li;Xuefeng Wang;Weiyang Sun;Na Feng;Songtao Yang;Xianzhu Xia;Ningyi Jin;Yifa Zhou;Yuwei Gao

作者机构:College of Life SciencesNortheast Normal UniversityChangchunJilin130021China Changchun Veterinary Research InstituteChinese Academy of Agricultural Sciences.Changchun130122China College of Animal MedicineJilin UniversityChangchun130000China College of Basic MedicineChangchun University of Chinese MedicineChangchun130117China College of Animal Science and TechnologyJilin Agricultural UniversityChangchun130033China College of Life SciencesShandong Normal UniversityJinan250014China 

出 版 物:《Virologica Sinica》 (中国病毒学(英文版))

年 卷 期:2023年第38卷第1期

页      面:119-127页

核心收录:

学科分类:090603[农学-临床兽医学] 0710[理学-生物学] 09[农学] 0906[农学-兽医学] 

基  金:supported by the Chinese National Natural Science Foundation of China(grant number:31970502) the National Key Research and Development Program of China(2021YFC2301701,2020ZX10001-016-003 and ZX10304402-003-006). 

主  题:Influenza viruses H5N1 Taurolidine(TRD) Cytokine storms Inflammatory response NF-κB signaling pathway 

摘      要:Taurolidine(TRD),a derivative of taurine,has anti-bacterial and anti-tumor effects by chemically reacting with cell-walls,endotoxins and exotoxins to inhibit the adhesion of microorganisms.However,its application in antiviral therapy is seldom reported.Here,we reported that TRD significantly inhibited the replication of influenza virus H5N1 in MDCK cells with the half-maximal inhibitory concentration(EC_(50))of 34.45μg/mL.Furthermore,the drug inhibited the amplification of the cytokine storm effect and improved the survival rate of mice lethal challenged with H5N1(protection rate was 86%).Moreover,TRD attenuated virus-induced lung damage and reduced virus titers in mice lungs.Administration of TRD reduced the number of neutrophils and increased the number of lymphocytes in the blood of H5N1 virus-infected mice.Importantly,the drug regulated the NF-κB signaling pathway by inhibiting the separation of NF-κB and IκBa,thereby reducing the expression of inflammatory factors.In conclusion,our findings suggested that TRD could act as a potential anti-influenza drug candidate in further clinical studies.

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