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研究人员已经绘制出第一幅关键的冠状病毒蛋白的3D地图

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2020年02月26日

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Researchers Have Created The First 3D Map Of A Key Coronavirus Protein

研究人员已经绘制出第一幅关键的冠状病毒蛋白的3D地图

A team of scientists from the University of Texas at Austin and the National Institutes of Health have produced the first 3D atomic-scale map of a key protein used by 2019-nCoV, the new coronavirus that infects humans. The discovery could be vital in the production of an effective vaccine against the disease.

德克萨斯大学奥斯汀分校和美国国立卫生研究院的一组科学家绘制出了2019年ncov(一种感染人类的新型冠状病毒)使用的一种关键蛋白质的首个三维原子尺度地图。这一发现对于生产有效的疫苗来对抗这种疾病是至关重要的。

 


Alfredo Carpineti

The team mapped a part of the virus called a spike protein that attaches itself to human cells and infects them. The study, published in Science, details the protein structure, indicating its similarities and differences with the SARS coronavirus. The work also reveals that the antibodies for SARS are not effective against the new virus.

研究小组绘制了病毒的一个叫做“刺突蛋白”的部分,它附着在人类细胞上并感染人类细胞。这项发表在《科学》杂志上的研究详细描述了这种蛋白质结构,指出了它与SARS冠状病毒的异同。这项工作还表明,SARS抗体对这种新病毒无效。

The team obtained the structure so quickly thanks to their experience studying other coronaviruses such as SARS-CoV and MERS-CoV. This allowed them to use methods already in place to lock the spike proteins to better analyze them.

研究小组通过对其他冠状病毒如SARS-CoV和MERS-CoV的研究,很快就获得了这种结构。这使得他们能够使用现有的方法来锁定穗蛋白,从而更好地分析它们。

“As soon as we knew this was a coronavirus, we felt we had to jump at it,” senior author Jason McLellan, an associate professor at UT Austin, said in a statement. “because we could be one of the first ones to get this structure. We knew exactly what mutations to put into this, because we’ve already shown these mutations work for a bunch of other coronaviruses.”

“当我们得知这是一种冠状病毒时,我们觉得必须马上采取行动,”该研究的资深作者、德克萨斯大学奥斯汀分校的副教授杰森·麦克莱伦在一份声明中说。“因为我们可能是最先获得这种结构的公司之一。我们确切地知道应该加入什么,因为我们已经证明这些突变对其他一些冠状病毒也有效。”

The discovery was possible thanks to the cryogenic electron microscopy (cryo-EM) technique. With this, samples are cooled down to -150℃ and then bombarded with a stream of electrons. By registering how these electrons bounce around, the team can reconstruct the 3D shape of the molecules.

由于低温电子显微镜技术,这一发现成为可能。这样,样品被冷却到-150℃,然后被电子流轰击。通过记录这些电子是如何弹来弹去的,研究小组可以重建分子的三维形状。

The work confirms independent analyses that suggest the entry point of the 2019-nCoV into human cells is the ACE2 receptor. This was also the case for SARS, but the new virus has 10 times the affinity for this receptor than the SARS coronavirus. It's possible this affinity could be contributing to the new coronavirus' ability to transmit between humans so easily, although the authors warn that more studies are needed to be certain.

这项工作证实了一些独立的分析,这些分析表明2019-nCoV进入人类细胞的切入点是ACE2受体。SARS也是如此,但是这种新病毒对这种受体的亲和力是SARS冠状病毒的10倍。这种亲缘关系可能有助于这种新型冠状病毒在人与人之间如此轻易地传播,不过作者警告说,还需要更多的研究来证实这一点。

The spike protein has two conformations (or two shapes) – one before it infects the host cells and one during the infection. The team created a map of the pre-infection shape of the protein (pictured above), also known as the prefusion conformation.

穗蛋白有两种构象(或两种形状)——一种在感染宿主细胞之前,另一种在感染过程中。研究小组绘制了一幅感染前蛋白质形状的地图(见上图),也被称为融合前构象。

Since the team managed to reconstruct molecules on the spike protein's surface, the part that produces an immune response, they now plan to use this to isolate the right antibodies in patients that have recovered from the infection. This could be used to treat a 2019-nCoV infection after exposure. While the work is encouraging, a successful vaccine is likely still many months, if not longer, away.

由于研究小组成功地重建了长钉蛋白表面的分子,即产生免疫反应的部分,他们现在计划用它来分离从感染中恢复的病人的正确抗体。这可以用于治疗暴露后2019-nCoV感染。虽然工作令人鼓舞,但成功的疫苗可能还需要好几个月,甚至更长时间。


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