《自然》：刺突蛋白变异让冠状病毒更具传染性

资讯作者：Duke University Medical Center 

编辑翻译：奇奇

译文校对：菁菁

本文献于2021年7月刊登在国际著名期刊《科学》（Science）上。文中杜克大学医学中心的研究人员发现新冠病毒变异体的突变机制不同，但都增强了病毒的传染性以及抵抗免疫的能力。

通过联合采用结构生物学和计算的方法，杜克大学领导的一个研究团队已经确定了SARS-CoV-2刺突蛋白的多个突变是如何独立产生变异的，而且这些变异让病毒传染性更强，以及有了抵御免疫抗体的可能。

通过获得刺突蛋白的突变，其他病毒变种独立演化的刺突变异增强了它们在人群中的快速传播以及抵御一些抗体的能力。研究人员已经将他们的发现刊登在了《自然》杂志上。

杜克人类疫苗研究所结构生物学部的主任、资深作者Priyamvada Acharya博士说：“病毒表面的刺突帮助SARS-CoV-2侵入宿主的细胞。”

“刺突蛋白的变化决定了病毒的传播能力，包括传播的程度和速度，” Acharya说，“世界范围内出现了几种变异SARS-CoV-2刺突，它们出现的时间不同，地点也不同，但它们的结果类似。在我们抗击病毒大流行中，了解这些刺突的变异机制很重要。”

 Acharya及其同事（包括第一作者Sophie Gobeil博士和通讯作者Rory Henderson博士）开发了结构模型来识别病毒刺突蛋白的变化。冷冻电子显微镜能够让原子水平可视化，当结合分析实验时能够让团队创造活病毒的模拟物，这与它在宿主细胞中的功能直接相关。该团队使用计算分析建立了模型，显示了结构机制的作用。

Henderson说:“通过构建刺突的架构，我们可以看到刺突是如何运动的，以及这种运动是如何随着突变而变化的。不同的刺突不会以相同的方式移动，但它们达到了相同的目的。首次出现在南非和巴西的变种是同一种机制，而英国和水貂的变种则是另一种机制。”

所有的变异都增强了病毒对宿主的影响能力，尤其是通过ACE2受体的变异。这些变化还产生了对抗体不那么敏感的病毒，即刺突变异的持续积累可能会降低现有疫苗的有效率，这引起了人们的担忧。

Gobeil认为这项研究揭示了冠状病毒的复杂性。她说：“令人惊讶的是，病毒以多种不同的方式变得更具传染性和侵入性。这也说明了大自然的适应性。”

英语原文

Study Reveals Mechanisms of Increased Infectivity and Antibody Resistance of SARS-CoV-2 Variants

Combining structural biology and computation, a Duke-led team of researchers has identified how multiple mutations on the SARS-CoV-2 spike protein independently create variants that are more transmissible and potentially resistant to antibodies.

By acquiring mutations on the spike protein, other variants independently developed spike mutations that enhanced their ability to spread rapidly in human populations and resist some antibodies. The researchers have published their findings in Science.

"The spike on the surface of the virus helps SARS-CoV-2 enter into host cells," said senior author Priyamvada Acharya, Ph.D., director of the Division of Structural Biology at the Duke Human Vaccine Institute.

"Changes on the spike protein determine transmissibility of the virus—how far and quickly it spreads," Acharya said. "Some variations of the SARS-CoV-2 spike are occurring at different times and different places throughout the world, but have similar results, and it's important to understand the mechanics of these spike mutations as we work to fight this pandemic."

Acharya and colleagues—including first author Sophie Gobeil, Ph.D, and co-corresponding author Rory Henderson, Ph.D.—developed structural models to identify changes in the virus's spike protein. Cryo-electron microscopy allowed atomic level visualization, while binding assays enabled the team to create mimics of the live virus that directly correlated with its function in host cells. From there, the team used computational analysis to build models that showed the structural mechanisms at work.

"By building a skeleton of the spike, we could see how the spike is moving, and how this movement changes with mutations," Henderson said. "The different variant spikes are not moving the same way, but they accomplish the same task. The variants first appearing in South Africa and Brazil use one mechanism, while the UK and the mink variants use another mechanism."

All the variants showed increased ability to bind to the host, notably via the ACE2 receptor. The changes also created viruses that were less susceptible to antibodies, raising concerns that continued accumulation of spike mutations may reduce the efficiency of current vaccines.

Gobeil said the research illuminated the complexity of the virus. "It's amazing how many different ways the virus comes up with to be more infectious and invasive," she said. "Nature is clever."

参考文献

Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity, Science (2021).

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