The Antihistamine Drugs Carbinoxamine Maleate and Chlorpheniramine Maleate Exhibit Potent Antiviral Activity Against a Broad Spectrum of Influenza Viruses.
The Antihistamine Drugs Carbinoxamine Maleate and Chlorpheniramine Maleate Exhibit Potent Antiviral Activity Against a Broad Spectrum of Influenza Viruses.
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抗组胺药马来酸卡比沙明和马来酸氯苯那敏对多种流感病毒表现出有效的抗病毒活性。
DOI：
10.3389/fmicb.2018.02643
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发表时间：
2018
影响因子：
5.2
通讯作者：
Jiang S
中科院分区：
文献类型：
--
作者：
Xu W;Xia S;Pu J;Wang Q;Li P;Lu L;Jiang S
甲型流感病毒（IAV）是人类中一些最常见的感染性病原体，它们在免疫功能低下的人群以及儿童和老年人中造成严重的死亡率和发病率。利用Cell Counting Kit-8细胞病变效应（CPE）还原法对fda批准的1280个药物文库进行筛选，发现马来酸卡比诺胺（CAM）和S-(+)-马来酸氯苯那敏（SCM）两种抗组胺药对A/Shanghai/4664T/2013（H7N9）感染具有较强的抗病毒活性，IC50（半最大抑制浓度）分别为3.56 μM和11.84 μM。进一步研究表明，CAM和SCM还能抑制A/Shanghai/37T/2009（H1N1）、A/Puerto Rico/8/1934（H1N1）、A/贵州/54/1989（H3N2）和B型流感病毒B/Shanghai/2017（by）的感染。小鼠鼻内感染A/H7N9/ 4664t /2013 （H7N9）病毒，腹腔注射CAM （10 mg/kg / d）或SCM (1 mg/kg / d) 5 d。A/Shanghai/4664T/2013（H7N9）完全保护CAM或SCM（每天10 mg/kg）免受感染。机制研究结果表明，两者均可通过阻断病毒进入病毒生命周期早期的靶细胞来抑制流感病毒感染。然而，CAM和SCM既不能阻断HA活性特征的病毒附着，也不能阻断NA活性特征的病毒释放。这些数据表明，这两种化合物可能干扰内吞过程。因此，我们已经确定了两种fda批准的抗组胺药，CAM和SCM，它们可以重新用于抑制不同甲型流感病毒株的感染，一种乙型流感病毒株有可能用于治疗和预防流感病毒感染。
Influenza A viruses (IAV) comprise some of the most common infectious pathogens in humans, and they cause significant mortality and morbidity in immunocompromised people as well as children and the elderly. After screening an FDA-approved drug library containing 1280 compounds by cytopathic effect (CPE) reduction assay using the Cell Counting Kit-8, we found two antihistamines, carbinoxamine maleate (CAM) and S-(+)-chlorpheniramine maleate (SCM) with potent antiviral activity against A/Shanghai/4664T/2013(H7N9) infection with IC50 (half-maximal inhibitory concentration) of 3.56 and 11.84 μM, respectively. Further studies showed that CAM and SCM could also inhibit infection by other influenza A viruses, including A/Shanghai/37T/2009(H1N1), A/Puerto Rico/8/1934(H1N1), A/Guizhou/54/1989(H3N2), and one influenza B virus, B/Shanghai/2017(BY). Mice were challenged intranasally with A/H7N9/4664T/2013 (H7N9) virus and intraperitoneally injected with CAM (10 mg/kg per day) or SCM (1 mg/kg per day) for 5 days. CAM or SCM (10 mg/kg per day) were fully protected against challenge with A/Shanghai/4664T/2013(H7N9). The results from mechanistic studies indicate that both could inhibit influenza virus infection by blocking viral entry into the target cell, the early stage of virus life cycle. However, CAM and SCM neither blocked virus attachment, characteristic of HA activity, nor virus release, characteristic of NA activity. Such data suggest that these two compounds may interfere with the endocytosis process. Thus, we have identified two FDA-approved antihistamine drugs, CAM and SCM, which can be repurposed for inhibiting infection by divergent influenza A strains and one influenza B strain with potential to be used for treatment and prevention of influenza virus infection.
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影响因子：
5.2
作者：
Droebner K;Haasbach E;Dudek SE;Scheuch G;Nocker K;Canisius S;Ehrhardt C;von Degenfeld G;Ludwig S;Planz O
通讯作者：
Planz O
影响因子：
8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Matsuzaki Y;Mizuta K;Aoki Y;Suto A;Abiko C;Sanjoh K;Sugawara K;Takashita E;Itagaki T;Katsushima Y;Ujike M;Obuchi M;Odagiri T;Tashiro M
通讯作者：
Tashiro M
影响因子：
3.5
作者：
DiMasi, JA;Hansen, RW;Grabowski, HG
通讯作者：
Grabowski, HG
影响因子：
4.9
作者：
Bergen, Phillip J.;Li, Jian;Nation, Roger L.
通讯作者：
Nation, Roger L.