tetano
Editor, Senior Moderator
Virol Sin
. 2022 Nov 27;S1995-820X(22)00194-8.
doi: 10.1016/j.virs.2022.11.010. Online ahead of print.
Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway
Chaoxiang Lv[SUP] 1 [/SUP], Yuanguo Li[SUP] 2 [/SUP], Tiecheng Wang[SUP] 3 [/SUP], Qiqi Zhang[SUP] 4 [/SUP], Jing Qi[SUP] 1 [/SUP], Mingwei Sima[SUP] 5 [/SUP], Entao Li[SUP] 3 [/SUP], Tian Qin[SUP] 1 [/SUP], Zhuangzhuang Shi[SUP] 6 [/SUP], Fangxu Li[SUP] 7 [/SUP], Xuefeng Wang[SUP] 3 [/SUP], Weiyang Sun[SUP] 3 [/SUP], Na Feng[SUP] 3 [/SUP], Songtao Yang[SUP] 3 [/SUP], Xianzhu Xia[SUP] 3 [/SUP], Ningyi Jin[SUP] 8 [/SUP], Yifa Zhou[SUP] 9 [/SUP], Yuwei Gao[SUP] 10 [/SUP]
Affiliations
Abstract
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[SUB]50[/SUB]) 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.
Keywords: H5N1; Influenza viruses; NF-κB signaling pathway; cytokine storms; inflammatory response; taurolidine (TRD).
. 2022 Nov 27;S1995-820X(22)00194-8.
doi: 10.1016/j.virs.2022.11.010. Online ahead of print.
Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway
Chaoxiang Lv[SUP] 1 [/SUP], Yuanguo Li[SUP] 2 [/SUP], Tiecheng Wang[SUP] 3 [/SUP], Qiqi Zhang[SUP] 4 [/SUP], Jing Qi[SUP] 1 [/SUP], Mingwei Sima[SUP] 5 [/SUP], Entao Li[SUP] 3 [/SUP], Tian Qin[SUP] 1 [/SUP], Zhuangzhuang Shi[SUP] 6 [/SUP], Fangxu Li[SUP] 7 [/SUP], Xuefeng Wang[SUP] 3 [/SUP], Weiyang Sun[SUP] 3 [/SUP], Na Feng[SUP] 3 [/SUP], Songtao Yang[SUP] 3 [/SUP], Xianzhu Xia[SUP] 3 [/SUP], Ningyi Jin[SUP] 8 [/SUP], Yifa Zhou[SUP] 9 [/SUP], Yuwei Gao[SUP] 10 [/SUP]
Affiliations
- PMID: 36450323
- DOI: 10.1016/j.virs.2022.11.010
Abstract
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[SUB]50[/SUB]) 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.
Keywords: H5N1; Influenza viruses; NF-κB signaling pathway; cytokine storms; inflammatory response; taurolidine (TRD).