Pharmacodynamics, Pharmacokinetics, and Antiviral Activity of BAY 81-8781, a Novel NF-κB Inhibiting Anti-influenza Drug.
Pharmacodynamics, Pharmacokinetics, and Antiviral Activity of BAY 81-8781, a Novel NF-κB Inhibiting Anti-influenza Drug.
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DOI：
10.3389/fmicb.2017.02130
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发表时间：
2017
影响因子：
5.2
通讯作者：
Planz O
中科院分区：
文献类型：
--
作者：
Droebner K;Haasbach E;Dudek SE;Scheuch G;Nocker K;Canisius S;Ehrhardt C;von Degenfeld G;Ludwig S;Planz O
流感是一种呼吸道疾病，每年都会流行。针对该病毒的抗病毒治疗方案是存在的，但其效果有限，而且流感病毒株很容易产生耐药性。因此，迫切需要新的治疗策略。在本研究中，我们研究了被批准作为静脉注射阿司匹林的 D,L-赖氨酸乙酰水杨酸盐·甘氨酸（BAY 81-8781；LASAG）的抗流感病毒特性。用于静脉注射。 BAY 81-8781 不是直接靶向病毒，而是抑制 NF-κB 通路的激活，这是流感病毒有效繁殖所必需的。使用高致病性禽流感病毒株，我们可以证明 BAY 81-8781 能够在体外控制流感病毒感染。在小鼠感染模型中，吸入 BAY 81-8781 导致肺部病毒滴度降低，并保护小鼠免受致命感染。药理学研究表明，口服给药途径不适合达到足以在肺部发挥抗病毒作用的 BAY 81-8781 浓度。 BAY 81-8781 对感染流感病毒的小鼠在感染后 48 小时开始治疗，仍能有效保护 50% 的动物免于死亡。总之，这些数据成功证明了新颖的创新抗病毒概念，即针对病毒传播所需的宿主细胞信号通路而不是病毒结构。
Influenza is a respiratory disease that causes annual epidemics. Antiviral treatment options targeting the virus exist, but their efficiency is limited and influenza virus strains easily develop resistance. Thus, new treatment strategies are urgently needed. In the present study, we investigated the anti-influenza virus properties of D,L-lysine acetylsalicylate ⋅ glycine (BAY 81-8781; LASAG) that is approved as Aspirin i.v. for intravenous application. Instead of targeting the virus directly BAY 81-8781 inhibits the activation of the NF-κB pathway, which is required for efficient influenza virus propagation. Using highly pathogenic avian influenza virus strains we could demonstrate that BAY 81-8781 was able to control influenza virus infection in vitro. In the mouse infection model, inhalation of BAY 81-8781 resulted in reduced lung virus titers and protection of mice from lethal infection. Pharmacological studies demonstrated that the oral route of administration was not suitable to reach the sufficient concentrations of BAY 81-8781 for a successful antiviral effect in the lung. BAY 81-8781 treatment of mice infected with influenza virus started as late as 48 h after infection was still effective in protecting 50% of the animals from death. In summary, the data represent a successful proof of the novel innovative antiviral concept of targeting a host cell signaling pathway that is required for viral propagation instead of viral structures.
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影响因子：
24.3
作者：
Herold, Susanne;Becker, Christin;Budinger, G. R. Scott
通讯作者：
Budinger, G. R. Scott
影响因子：
3.8
作者：
Nimmerjahn, F;Dudziak, D;Mautner, J
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Mautner, J
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3.4
作者：
Mazur, Igor;Wurzer, Walter J.;Ludwig, Stephan
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Ludwig, Stephan
影响因子：
2
作者：
Nagelschmitz, J.;Blunck, M.;Hohlfeld, T.
通讯作者：
Hohlfeld, T.
影响因子：
4.9
作者：
Yen, HL;Herlocher, LM;Govorkova, EA
通讯作者：
Govorkova, EA