Identification of an antioxidant small-molecule with broad-spectrum antiviral activity
Identification of an antioxidant small-molecule with broad-spectrum antiviral activity
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DOI：
10.1016/j.antiviral.2011.10.011
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发表时间：
2012-01-01
影响因子：
7.6
通讯作者：
Bavari, Sina
中科院分区：
文献类型：
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作者：
Panchal, Rekha G.;Reid, St. Patrick;Bavari, Sina
高度致命的丝状病毒，埃博拉病毒和马尔堡病毒在人类和非人类灵长类动物中引起严重的出血热。到目前为止，还没有获得许可的疫苗或治疗方法来对抗这些感染。识别在感染过程中发挥重要作用的新途径和宿主靶点将为开发治疗方法提供潜在靶点。埃博拉病毒抑制剂的小分子化学筛选导致鉴定出化合物NSC 62914。发现该化合物在基于细胞的测定中表现出抗丝状病毒活性，并在用埃博拉病毒或马尔堡病毒攻击后体内保护小鼠。此外，在基于细胞的试验中发现该化合物可抑制裂谷热病毒、拉沙病毒和委内瑞拉马脑炎病毒。对该化合物作用机制的研究表明，它具有抗氧化性能。具体而言，发现化合物NSC 62914充当活性氧物质的清除剂，并上调氧化应激诱导的基因。然而，四种已知的抗氧化剂化合物未能抑制丝状病毒感染，因此表明抗氧化剂NSC 62914的抗病毒功能的机制基础可能涉及多种信号传导途径/靶点的调节。由爱思唯尔公司出版
The highly lethal filoviruses, Ebola and Marburg cause severe hemorrhagic fever in humans and non-human primates. To date there are no licensed vaccines or therapeutics to counter these infections. Identifying novel pathways and host targets that play an essential role during infection will provide potential targets to develop therapeutics. Small molecule chemical screening for Ebola virus inhibitors resulted in identification of a compound NSC 62914. The compound was found to exhibit anti-filovirus activity in cell-based assays and in vivo protected mice following challenge with Ebola or Marburg viruses. Additionally, the compound was found to inhibit Rift Valley fever virus, Lassa virus and Venezuelan equine encephalitis virus in cell-based assays. Investigation of the mechanism of action of the compound revealed that it had antioxidant properties. Specifically, compound NSC 62914 was found to act as a scavenger of reactive oxygen species, and to up-regulate oxidative stress-induced genes. However, four known antioxidant compounds failed to inhibit filovirus infection, thus suggesting that the mechanistic basis of the antiviral function of the antioxidant NSC 62914 may involve modulation of multiple signaling pathways/targets. Published by Elsevier B.V.