Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lv, Chaoxiang, Li, Yuanguo, Wang, Tiecheng, Zhang, Qiqi, Qi, Jing, Sima, Mingwei, Li, Entao, Qin, Tian, Shi, Zhuangzhuang, Li, Fangxu, Wang, Xuefeng, Sun, Weiyang, Feng, Na, Yang, Songtao, Xia, Xianzhu, Jin, Ningyi, Zhou, Yifa, Gao, Yuwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wuhan Institute of Virology, Chinese Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006309/
https://www.ncbi.nlm.nih.gov/pubmed/36450323
http://dx.doi.org/10.1016/j.virs.2022.11.010
_version_ 1784905281266778112
author Lv, Chaoxiang
Li, Yuanguo
Wang, Tiecheng
Zhang, Qiqi
Qi, Jing
Sima, Mingwei
Li, Entao
Qin, Tian
Shi, Zhuangzhuang
Li, Fangxu
Wang, Xuefeng
Sun, Weiyang
Feng, Na
Yang, Songtao
Xia, Xianzhu
Jin, Ningyi
Zhou, Yifa
Gao, Yuwei
author_facet Lv, Chaoxiang
Li, Yuanguo
Wang, Tiecheng
Zhang, Qiqi
Qi, Jing
Sima, Mingwei
Li, Entao
Qin, Tian
Shi, Zhuangzhuang
Li, Fangxu
Wang, Xuefeng
Sun, Weiyang
Feng, Na
Yang, Songtao
Xia, Xianzhu
Jin, Ningyi
Zhou, Yifa
Gao, Yuwei
author_sort Lv, Chaoxiang
collection PubMed
description 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 34.45 ​μg/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.
format Online
Article
Text
id pubmed-10006309
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Wuhan Institute of Virology, Chinese Academy of Sciences
record_format MEDLINE/PubMed
spelling pubmed-100063092023-03-12 Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway Lv, Chaoxiang Li, Yuanguo Wang, Tiecheng Zhang, Qiqi Qi, Jing Sima, Mingwei Li, Entao Qin, Tian Shi, Zhuangzhuang Li, Fangxu Wang, Xuefeng Sun, Weiyang Feng, Na Yang, Songtao Xia, Xianzhu Jin, Ningyi Zhou, Yifa Gao, Yuwei Virol Sin Research Article 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 34.45 ​μg/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. Wuhan Institute of Virology, Chinese Academy of Sciences 2022-11-28 /pmc/articles/PMC10006309/ /pubmed/36450323 http://dx.doi.org/10.1016/j.virs.2022.11.010 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Lv, Chaoxiang
Li, Yuanguo
Wang, Tiecheng
Zhang, Qiqi
Qi, Jing
Sima, Mingwei
Li, Entao
Qin, Tian
Shi, Zhuangzhuang
Li, Fangxu
Wang, Xuefeng
Sun, Weiyang
Feng, Na
Yang, Songtao
Xia, Xianzhu
Jin, Ningyi
Zhou, Yifa
Gao, Yuwei
Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway
title Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway
title_full Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway
title_fullStr Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway
title_full_unstemmed Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway
title_short Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway
title_sort taurolidine improved protection against highly pathogenetic avian influenza h5n1 virus lethal-infection in mouse model by regulating the nf-κb signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006309/
https://www.ncbi.nlm.nih.gov/pubmed/36450323
http://dx.doi.org/10.1016/j.virs.2022.11.010
work_keys_str_mv AT lvchaoxiang taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT liyuanguo taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT wangtiecheng taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT zhangqiqi taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT qijing taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT simamingwei taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT lientao taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT qintian taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT shizhuangzhuang taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT lifangxu taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT wangxuefeng taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT sunweiyang taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT fengna taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT yangsongtao taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT xiaxianzhu taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT jinningyi taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT zhouyifa taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway
AT gaoyuwei taurolidineimprovedprotectionagainsthighlypathogeneticavianinfluenzah5n1viruslethalinfectioninmousemodelbyregulatingthenfkbsignalingpathway