研究人員已經(jīng)繪制出第一幅關(guān)鍵的冠狀病毒蛋白的3D地圖

研究人員已經(jīng)繪制出第一幅關(guān)鍵的冠狀病毒蛋白的3D地圖

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.

德克薩斯大學奧斯汀分校和美國國立衛(wèi)生研究院的一組科學家繪制出了2019年ncov(一種感染人類的新型冠狀病毒)使用的一種關(guān)鍵蛋白質(zhì)的首個三維原子尺度地圖。這一發(fā)現(xiàn)對于生產(chǎn)有效的疫苗來對抗這種疾病是至關(guān)重要的。

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.

研究小組繪制了病毒的一個叫做“刺突蛋白”的部分，它附著在人類細胞上并感染人類細胞。這項發(fā)表在《科學》雜志上的研究詳細描述了這種蛋白質(zhì)結(jié)構(gòu)，指出了它與SARS冠狀病毒的異同。這項工作還表明，SARS抗體對這種新病毒無效。

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.

研究小組通過對其他冠狀病毒如SARS-CoV和MERS-CoV的研究，很快就獲得了這種結(jié)構(gòu)。這使得他們能夠使用現(xiàn)有的方法來鎖定穗蛋白，從而更好地分析它們。

“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.”

“當我們得知這是一種冠狀病毒時，我們覺得必須馬上采取行動，”該研究的資深作者、德克薩斯大學奧斯汀分校的副教授杰森·麥克萊倫在一份聲明中說。“因為我們可能是最先獲得這種結(jié)構(gòu)的公司之一。我們確切地知道應(yīng)該加入什么，因為我們已經(jīng)證明這些突變對其他一些冠狀病毒也有效。”

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.

由于低溫電子顯微鏡技術(shù)，這一發(fā)現(xiàn)成為可能。這樣，樣品被冷卻到-150℃，然后被電子流轟擊。通過記錄這些電子是如何彈來彈去的，研究小組可以重建分子的三維形狀。

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.

這項工作證實了一些獨立的分析，這些分析表明2019-nCoV進入人類細胞的切入點是ACE2受體。SARS也是如此，但是這種新病毒對這種受體的親和力是SARS冠狀病毒的10倍。這種親緣關(guān)系可能有助于這種新型冠狀病毒在人與人之間如此輕易地傳播，不過作者警告說，還需要更多的研究來證實這一點。

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.

穗蛋白有兩種構(gòu)象(或兩種形狀)——一種在感染宿主細胞之前，另一種在感染過程中。研究小組繪制了一幅感染前蛋白質(zhì)形狀的地圖(見上圖)，也被稱為融合前構(gòu)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.

由于研究小組成功地重建了長釘?shù)鞍妆砻娴姆肿?，即產(chǎn)生免疫反應(yīng)的部分，他們現(xiàn)在計劃用它來分離從感染中恢復的病人的正確抗體。這可以用于治療暴露后2019-nCoV感染。雖然工作令人鼓舞，但成功的疫苗可能還需要好幾個月，甚至更長時間。