Germacrone inhibits early stages of influenza virus infection

Germacrone inhibits early stages of influenza virus infection
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DOI:
10.1016/j.antiviral.2013.09.021
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发表时间:
2013-12-01
期刊:
影响因子:
7.6
通讯作者:
Chen, Xulin
Chen, Xulin
中科院分区:
医学2区
文献类型:
--
作者:
Liao, Qingjiao;Qian, Zhengxu;Chen, Xulin

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高致病性流感病毒对人类构成严重的公共卫生威胁。虽然疫苗是可用的,但由于出现耐药病毒株,需要抗病毒药物来有效控制疾病进展和病毒传播。本研究发现莪术精油的主要成分莪术酮具有抑制流感病毒复制的作用。germacron对H1N1和H3N2甲型流感病毒和乙型流感病毒的抗病毒活性呈剂量依赖性。germacron处理后,MDCK和A549细胞的病毒蛋白表达、RNA合成和感染性子代病毒的产生均降低。在一项添加时间研究中,发现德国马克龙在附着/进入步骤和病毒复制周期的早期阶段都表现出抑制作用。germacron还显示出对小鼠致命感染的有效保护,并降低了肺中的病毒滴度。此外,germacone和oseltamivir联合使用在体外和体内均表现出抑制流感病毒感染的叠加效应。我们的研究结果表明,德国宏酮可能有潜力作为一种治疗药物单独或与其他药物联合治疗流感病毒感染。(C) 2013 Elsevier B.V.版权所有
Highly pathogenic influenza viruses pose a serious public health threat to humans. Although vaccines are available, antivirals are needed to efficiently control disease progression and virus transmission due to the emergence of drug-resistant viral strains. In this study, germacrone, which is a major component of the essential oils extracted from Rhizoma Curcuma, was found to inhibit influenza virus replication. Germacrone showed antiviral activity against the H1N1 and H3N2 influenza A viruses and the influenza B virus in a dose-dependent manner. The viral protein expression, RNA synthesis and the production of infectious progeny viruses were decreased both in MDCK and A549 cells treated with germacrone. In a time-of-addition study, germacrone was found to exhibit an inhibitory effect on both the attachment/entry step and the early stages of the viral replication cycle. Germacrone also exhibited an effective protection of mice from lethal infection and reduced the virus titres in the lung. Furthermore, the combination of germacrone and oseltamivir exhibited an additive effect on the inhibition of influenza virus infection, both in vitro and in vivo. Our results suggest that germacrone may have the potential to be developed as a therapeutic agent alone or in combination with other agents for the treatment of influenza virus infection. (C) 2013 Elsevier B.V. All rights reserved.