Anti-influenza activity of c60 fullerene derivatives.
Anti-influenza activity of c60 fullerene derivatives.
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DOI：
10.1371/journal.pone.0066337
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kuzuhara T
中科院分区：
文献类型：
--
作者：
Shoji M;Takahashi E;Hatakeyama D;Iwai Y;Morita Y;Shirayama R;Echigo N;Kido H;Nakamura S;Mashino T;Okutani T;Kuzuhara T
起源于猪的H1N1甲型流感病毒于2009年引起全球大流行，高致病性H5 N1禽流感病毒近年来也在东南亚引起流行。因此，来自甲型流感的威胁仍然是严重的全球健康问题，并且非常需要靶向这些病毒的新型药物。甲型流感病毒RNA聚合酶由PA、PB 1和PB 2亚基组成，PA亚基的N-末端结构域具有核酸内切酶活性。富勒烯（C60）是一种独特的碳分子，形成一个球体。为了鉴定潜在的新的抗流感化合物，我们使用体外PA核酸内切酶抑制测定筛选了12个富勒烯衍生物。我们确定了8富勒烯衍生物，抑制核酸内切酶活性的PA N-末端结构域或全长PA蛋白在体外。我们还进行了C60富勒烯和PA核酸内切酶的计算机模拟对接分析，这表明富勒烯可以结合到PA核酸内切酶的活性口袋。在细胞培养系统中，我们发现几种富勒烯衍生物抑制甲型流感病毒感染和甲型流感病毒核蛋白和非结构蛋白1的表达。这些结果表明，富勒烯衍生物是开发新型抗流感药物的可能候选者。
The H1N1 influenza A virus, which originated in swine, caused a global pandemic in 2009, and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. Thus, the threat from influenza A remains a serious global health issue, and novel drugs that target these viruses are highly desirable. Influenza A RNA polymerase consists of the PA, PB1, and PB2 subunits, and the N-terminal domain of the PA subunit demonstrates endonuclease activity. Fullerene (C60) is a unique carbon molecule that forms a sphere. To identify potential new anti-influenza compounds, we screened 12 fullerene derivatives using an in vitro PA endonuclease inhibition assay. We identified 8 fullerene derivatives that inhibited the endonuclease activity of the PA N-terminal domain or full-length PA protein in vitro. We also performed in silico docking simulation analysis of the C60 fullerene and PA endonuclease, which suggested that fullerenes can bind to the active pocket of PA endonuclease. In a cell culture system, we found that several fullerene derivatives inhibit influenza A viral infection and the expression of influenza A nucleoprotein and nonstructural protein 1. These results indicate that fullerene derivatives are possible candidates for the development of novel anti-influenza drugs.
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影响因子：
3.7
作者：
Iwai Y;Murakami K;Gomi Y;Hashimoto T;Asakawa Y;Okuno Y;Ishikawa T;Hatakeyama D;Echigo N;Kuzuhara T
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Kuzuhara T
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通讯作者：
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