The NF-kappaB inhibitor SC75741 protects mice against highly pathogenic avian influenza A virus
The NF-kappaB inhibitor SC75741 protects mice against highly pathogenic avian influenza A virus
复制标题
DOI：
10.1016/j.antiviral.2013.06.008
复制
发表时间：
2013-09-01
影响因子：
7.6
通讯作者：
Planz, Oliver
中科院分区：
文献类型：
--
作者：
Haasbach, Emanuel;Reiling, Sarah Julia;Planz, Oliver
H1N1大流行性病毒和H5N1高致病性禽流感病毒在人类中的出现，以及对神经氨酸酶抑制剂具有耐药性的季节性H1N1变异体的出现，突出表明迫切需要新的和充分可用的抗病毒药物。我们和其他人已经证明流感病毒滥用细胞IKK/NF-kappaB信号通路进行有效复制，这表明该模块可能是抗病毒干预的合适靶点。本研究表明，新型NF-kappaB抑制剂SC75741可显著保护小鼠免受H5N1和H7N7亚型高致病性禽流感病毒感染。当SC75741以5mg /kg/天的浓度静脉注射时，治疗是有效的。此外，SC75741通过腹腔注射具有很高的生物利用度，并且在每天15 mg/kg或每天两次7.5 mg/kg的情况下对流感也有效。在感染前或感染后连续7天给予SC75741，达到保护作用。在保护小鼠免受流感病毒感染所需的浓度下，SC75741治疗未显示出不利影响。尽管需要更多的临床前研究，但SC75741可能是一种有希望的新型抗病毒药物，它针对的是宿主细胞而不是病毒本身。(C) 2013 Elsevier B.V.版权所有
The appearance of pandemic H1N1 and highly pathogenic avian H5N1 viruses in humans as well as the emergence of seasonal H1N1 variants resistant against neuraminidase inhibitors highlight the urgent need for new and amply available antiviral drugs. We and others have demonstrated that influenza virus misuses the cellular IKK/NF-kappaB signaling pathway for efficient replication suggesting that this module may be a suitable target for antiviral intervention. Here, we show that the novel NF-kappaB inhibitor SC75741 significantly protects mice against infection with highly pathogenic avian influenza A viruses of the H5N1 and H7N7 subtypes. Treatment was efficient when SC75741 was given intravenously in a concentration of 5 mg/kg/day. In addition, application of SC75741 via the intraperitoneal route resulted in a high bioavailability and was also efficient against influenza when given 15 mg/kg/day or 7.5 mg/kg/twice a day. Protection was achieved when SC75741 was given for seven consecutive days either prior to infection or as late as four days after infection. SC75741 treatment showed no adverse effects in the concentrations required to protect mice against influenza virus infection. Although more pre-clinical studies are needed SC75741 might be a promising candidate for a novel antiviral drug against influenza viruses that targets the host cell rather than the virus itself. (C) 2013 Elsevier B.V. All rights reserved.