氨溴索,又称“氨溴索”,是一种润滑和祛痰呼吸道的药物,临床上常用于急慢性支气管炎等疾病现在,中国科学家已经发现了通过人工智能药物靶标筛选来治疗新冠状病毒(2019-nCoV)的潜力。超过
的结果来自北京大学基础医学院王跃丹和朱明的团队。1月25日,该团队宣布,在了解新冠状病毒2019-nCoV的功能受体后,采用自主研发的人工智能药物靶标筛选系统,重点对2674种上市药物和1500种中药提取物进行药物筛选,发现了多种有望治疗新冠状病毒感染所致肺炎的潜在药物,包括常用药物沐舒坦等。
王跃丹现任北京大学卫生科学中心基础医学院免疫学系副主任、医学系生物医学实验教学中心副主任、病原与免疫学综合实验室主任。参与“非典分子病理学和免疫学发病机制研究”项目,获得教育部高等教育2007年自然科学奖(一等奖)
王跃丹和楚明团队的药物筛选依据来自1月21日的一篇轰动性论文中国科学院上海巴斯德研究所研究员郝培与中国军事医学研究所国家紧急预防控制药物工程技术研究中心研究员钟武和中国科学院分子植物科学卓越与创新中心研究员李璇合作,在《中国科学:生命科学》上发表了一篇在线文章,揭示了武汉新冠状病毒的进化起源及其感染的分子途径
在以前的论文中,研究人员发现新的冠状病毒刺突蛋白中与人血管紧张素转换酶2蛋白结合的5个关键氨基酸中的4个发生了变化,但这些变化的氨基酸总体上完美地保持了SARS-CoV S蛋白与血管紧张素转换酶2蛋白相互作用的原始结构构象针对
,作者在文章中解释说,尽管新冠状病毒的新结构和ACE2蛋白之间的相互作用能力由于一些氢键的丢失而降低,但它仍然达到了强结合自由能。这意味着人体内的ACE2蛋白在病毒感染中起着关键作用。
ACE2是肾素-血管紧张素-醛固酮系统(RAS)的关键分子,也是在包括肺泡上皮细胞在内的多种人类细胞表面表达的重要分子之一。2003年,血管紧张素转换酶2被确定为非典冠状病毒的功能性受体在
锁定受体ACE2蛋白后,王跃丹和楚明的团队使用人工智能药物靶标筛选系统对市场上的药物进行筛选,从而发现了许多潜在的药物
但是为什么只有氨溴索被释放?北京大学基础医学院副教授楚明在接受《中国科学》采访时表示,经过综合考虑,他们认为沐舒坦是呼吸科常用药物,毒副作用相对较低,可考虑在临床治疗中先行观察。与此同时,他们还发现了一些激素类药物,这些药物需要进一步澄清,因为他们不想引起临床问题,而且还没有发布。值得注意的是,1月25日,中国科学院上海医学研究所也宣布筛选出一批潜在药物。
由姜华良院士、饶院士牵头,中国科学院上海医学研究所和上海科技大学上海免疫化学研究所联合应急小组在20多个研究小组的参与下,筛选出30种具有治疗潜力的药物。这30种药物包括12种抗艾滋病病毒药物、2种抗呼吸道合胞病毒药物、几种活性天然产物和中药
研究团队利用以往抗非典药物研究积累的经验,开展了抗2019-nCoV药物研究。2003年非典爆发后,饶果断推动多党合作,组建了一个有效的“非典研究团队”。仅用了一个月的时间,就首次对SARS冠状病毒蛋白酶的三维结构进行了分析,为抗SARS研究奠定了科学基础。
具体来说,饶何姿和杨海涛的团队快速表达2019-nCoV水解酶(Mpro)并获得高分辨率晶体结构。在此基础上,联合小组综合运用虚拟筛选和酶学检测相结合的策略,重点对上市药物进行药物筛选,并自建“高效化合物数据库”和“药用植物化合物数据库”。30种药物、活性天然产物和中药可能对2019-nCoV有治疗作用,并迅速被发现。建议在临床治疗2019-nCoV感染肺炎患者时予以考虑和重视。
饶、队与王跃丹、楚明队的筛选思路有什么不同?楚明说,病毒进入人体后,通过与受体结合来感染细胞。我们的方法针对的是病毒的受体,即病毒进入细胞的大门,这相当于关闭了病毒进入细胞的大门。然而,中国科学院医学研究所为病毒本身筛选药物,即病毒分泌的水解酶。药物选择因目标不同而不同。
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