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Science: 小分子JNJ4796有望抑制多种流感病毒

  在一项新的研究中,来自荷兰、美国和比利时的研究人员发现了一种模拟广泛中和抗体行为的小分子。相关研究结果发表在 2019 年 3 月 8 日的 Science 期刊上,论文标题为“A small-molecule fusion inhibitor of influenza virus is orally active in mice”。在这篇论文中,他们描述了他们对这种分子的研究以及它在小鼠体内抵抗流感方面的作用。

science.png

图片来自Wilson lab


   当前,流感疫苗的作用机制是刺激免疫系统,提醒它需要比身体更快地产生抗体,这让身体几乎立即开始抵抗感染,阻止这种感染变得严重。但是大多数人都知道,疫苗仅含有一定数量的被杀死的流感病毒,这意味着那些接种疫苗的人仍然面临其他流感病毒变异株感染的风险。之前的研究已表明一般的抗流感抗体仅能够靶向一种流感病毒变异株。但是近期的研究表明,还有其他类型的抗体在发挥作用,它们能够靶向一种以上的流感病毒变异株,因而被称为广泛中和抗体。迄今为止,构建触发这类抗体产生的疫苗的研究工作尚未取得很大成功。但是,它们导致以类似方式与流感病毒结合的蛋白的产生。在这项新的研究中,这些研究人员发现了一种模拟这类蛋白行为的小分子,不过它的优点是能够在体内存活足够长时间,从而足以找到流感病毒并阻止它。

  为了找到这种分子,这些研究人员首先使用一种名为HB80.4的蛋白,这种蛋白经证实能够与流感病毒结合,而且对它的密切研究揭示了它的结合机制。他们利用这些信息筛选了 50 多万个小分子,旨在一种寻找能够以同样方式与流感病毒结合的小分子。最终,他们找到了一种称为 JNJ4796 的小分子。

这些研究人员将这种分子以药片的形式给予感染了大剂量流感病毒的小鼠,从而对它进行测试。他们报道测试组中没有一只小鼠死亡,而对照组中的一半小鼠死掉了。他们还报道这种分子能够中和人类支气管细胞中的流感病毒。


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