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MOL THER| 妙!科学家发现咀嚼含有ACE2蛋白的口香糖或减少SARS-CoV-2传播

2022-01-20 细胞 细胞

口香糖可能作为这场斗争中的一种额外工具。

在一项新的研究中,来自美国宾夕法尼亚大学和威斯达研究所的研究人员发现一种掺有植物产生的蛋白的口香糖可以用作捕获SARS-CoV-2病毒的诱饵,减少唾液中的病毒载量,并有可能抑制传播。这一发现可能会在对抗COVID-19大流行病的武器库中产生一种低成本的工具。相关研究结果近期发表在Molecular Therapy期刊上,论文标题为Debulking SARS-CoV-2 in saliva using angiotensin converting enzyme 2 in chewing gum to decrease oral virus transmission and infection”

论文通讯作者、宾夕法尼亚大学牙医学院的Henry Daniell说,“SARS-CoV-2在唾液腺中复制。我们知道当被感染的人打喷嚏、咳嗽或说话时,一些病毒会被排出并到达其他人的口腔中。这种口香糖提供了一个中和唾液中这种病毒的机会,给我们提供了一种可能减少疾病传播源的简单方法。”

针对COVID-19的疫苗接种有助于改变了这种大流行病的进程,但并没有阻止传播。即使是完全接种了疫苗的人仍然可以感染SARS-CoV-2,而且根据近期的研究,可能携带与未接种疫苗的人相似的病毒载量。

在这次大流行之前,Daniell一直在研究用于治疗高血压血管紧张素转化酶2(ACE2)。他的实验室使用一种获得专利的植物生产系统制造这种蛋白,以及其他许多可能具有治疗潜力的蛋白。通过用编码靶蛋白的DNA轰击植物材料,他们诱导植物叶绿体摄取DNA并开始产生靶蛋白。经过冻干和研磨的植物材料可以作为递送蛋白的一种手段。这种系统有可能避免蛋白药物合成的常见障碍:昂贵的生产和纯化过程。

Daniell过去在ACE2方面的研究工作在COVID-19大流行的背景下被证明是幸运的。人体细胞表面上的ACE2受体恰好也能结合SARS-CoV-2的刺突蛋白。其他研究小组已经表明,注射ACE2可以减少严重感染者的病毒载量。

与此同时,Daniell和宾夕法尼亚州牙科医生的同事Hyun(Michel)Koo的另一项研究工作涉及开发一种注入植物产生的蛋白的口香糖,以破坏牙菌斑。将他对ACE2的新见解与这种技术结合起来,Daniell想知道这种注入了植物产生的ACE2蛋白的口香糖是否能中和口腔中的SARS-CoV-2。

 

图片
图片来自Molecular Therapy, 2021, doi:10.1016/j.ymthe.2021.11.008。

为了找到答案,他联系了宾夕法尼亚大学佩雷尔曼医学院的Ronald Collman。Collman是一位病毒学家和肺部及重症监护医生,他的团队从这种大流行病的早期阶段就开始收集COVID-19患者的血液、鼻拭子、唾液和其他生物样本用于科学研究。

Collman说,“Daniell联系了我,问我们是否有样本来测试他的方法,什么样本适合测试,以及我们是否可以在内部验证唾液样本中的SARS-CoV-2病毒水平。这导致了在我们的微生物组研究基础上的跨校合作。”

为了测试这种口香糖,该团队让植物产生ACE2蛋白,并将它与另一种能使这种蛋白穿过粘膜屏障并促进结合的化合物配对,并将由此产生的植物材料整合到肉桂味的口香糖片中。将从COVID-19阳性患者的鼻咽拭子中获得的样本与这种口香糖一起孵化,结果发现表明口香糖中存在的ACE2可以中和SARS-CoV-2病毒。

在取得这些初步结果之后,这些作者进行了其他调查,比如对比SARS-CoV-2致病性低的病毒进行基因改造使之表达SARS-CoV-2刺突蛋白。他们观察到,这种口香糖通过阻断细胞表面上的ACE2受体或直接与刺突蛋白结合在很大程度上阻止了这种病毒或病毒颗粒进入细胞

最后,这些作者将COVID-19患者的唾液样本暴露在这种含有ACE2的口香糖中,发现SARS-CoV-2 RNA水平急剧下降,几乎无法检测到。

他们目前正在努力获得进行临床试验的许可,以评估该方法在感染SARS-CoV-2的人群中测试时是否安全和有效。

Collman说,“Daniell在植物中制造蛋白并口服使用的方法是廉价的,有望是可扩展的;它真地很不错。”

虽然这项研究仍处于早期开发阶段,但是如果临床试验证实这种口香糖是安全和有效的,那么就可能给那些感染状况不明的患者使用,甚至在必须摘掉口罩的牙科检查中使用,以减少将这种病毒传给护理人员的可能性。

Daniell说,“我们已经在使用口罩和其他物理屏障来减少传播的机会。这种口香糖可以作为这场斗争中的一种额外工具。”

原始出处

Debulking SARS-CoV-2 in saliva using angiotensin converting enzyme 2 in chewing gum to decrease oral virus transmission and infection.Molecular Therapy.2021, doi:10.1016/j.ymthe.2021.11.008

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    2022-08-08 hukaixun
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    2022-04-02 Boyinsh
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    2022-07-04 shanyongle
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    2022-01-22 小刀医生
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