Omicron刺突蛋白已完成冷冻电镜结构解析

2022-01-26 09:37 水木未来

研究人员进行了中和测定，并表明显示Omicron刺突蛋白的假病毒表现出增加的免疫逃逸。

以下内容转载自：GEN News

Omicron’s Spike Protein Captured via Cryo-Electron Microscopy

Omicron变体刺突蛋白与受体ACE2复合物的第一个分子水平结构解析现已发布。使用冷冻电子显微镜的近原子分辨率分析可以深入了解严重突变的Omicron变体如何附着并感染人类细胞。

The first molecular-level structural analysis of the Omicron variant spike protein in complex with human ACE2 is now available. The near-atomic resolution analysis—using cryo-electron microscopy—yields insights into how the heavily mutated Omicron variant attaches to and infects human cells.

这项工作发表在《科学》杂志上的论文 "SARS-CoV-2 Omicron变体：刺突蛋白-ACE2复合物的抗体逃逸和冷冻电镜结构" 。 DOI: 10.1126/science.abn7760 (2022)

This work is published in Science in the paper, “SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex.”

"了解病毒刺突蛋白的分子结构很重要，因为它将使我们能够在未来开发更有效的治疗Omicron和相关变体的治疗方法，"不列颠哥伦比亚大学生物化学和分子生物学教授Sriram Subramaniam博士说。"通过分析病毒感染人类细胞的机制，我们可以开发出更好的治疗方法，破坏这一过程并中和病毒。

“Understanding the molecular structure of the viral spike protein is important as it will allow us to develop more effective treatments against Omicron and related variants in the future,” said Sriram Subramaniam, PhD, professor of biochemistry and molecular biology at the University of British Columbia. “By analyzing the mechanisms by which the virus infects human cells, we can develop better treatments that disrupt that process and neutralize the virus.”

位于SARS-CoV-2外部的刺突蛋白使其能够进入人体细胞。Omicron变体在其刺突蛋白上有前所未有的37个突变 - 比以前的变体多三到五倍。

The spike protein, which is located on the outside of SARS-CoV-2, enables it to enter human cells. The Omicron variant has an unprecedented 37 mutations on its spike protein—three to five times more than previous variants.

结构分析显示，几种突变（R493，S496和R498）在刺突蛋白和人细胞受体ACE2之间产生了新的盐桥和氢键。研究人员指出，这些相互作用似乎补偿了其他Omicron突变，例如已知可降低ACE2结合亲和力的K417N，从而导致对Delta和Omicron变体的相似的生化ACE2结合亲和力。

The structural analysis revealed that several mutations (R493, S496, and R498) create new salt bridges and hydrogen bonds between the spike protein and the human cell receptor ACE2. The researchers noted that these interactions “appear to compensate for other Omicron mutations such as K417N known to reduce ACE2 binding affinity, resulting in similar biochemical ACE2 binding affinities for Delta and Omicron variants.”

与人类ACE2受体（蓝色）结合的Omicron变体刺突蛋白（紫色）的原子结构。[UBC医学系]

Atomic structure of the Omicron variant spike protein (purple) bound with the human ACE2 receptor (blue). [UBC Faculty of Medicine]

"总体而言，研究结果表明，Omicron比原始病毒具有更大的结合亲和力，其水平与我们在Delta变体中看到的水平更可比，"Subramaniam说。"值得注意的是，尽管发生了如此广泛的突变，Omicron变体仍保留了与人类细胞结合的能力。

“Overall, the findings show that Omicron has greater binding affinity than the original virus, with levels more comparable to what we see with the Delta variant,” said Subramaniam. “It is remarkable that the Omicron variant evolved to retain its ability to bind with human cells despite such extensive mutations.”

研究人员进行了中和测定，并表明显示Omicron刺突蛋白的假病毒表现出增加的免疫逃逸。与以前的变体相比，Omicron在所有测试的六种单克隆抗体中都显示出可测量的逃逸，并且完全逃逸了五种抗体。该变异还显示，从接种疫苗的个体和未接种疫苗的COVID-19患者中收集的抗体的逃逸率增加。

The researchers conducted neutralization assays and showed that pseudoviruses displaying the Omicron spike protein exhibit increased antibody evasion. In contrast to previous variants, Omicron showed measurable evasion from all six monoclonal antibodies tested, with complete escape from five. The variant also displayed increased evasion of antibodies collected from vaccinated individuals and unvaccinated COVID-19 patients.

"值得注意的是，与未接种疫苗的患者对自然感染的免疫力相比，Omicron对疫苗产生的免疫力的回避程度较低。这表明疫苗接种仍然是我们最好的防御措施，"Subramaniam说。

“Notably, Omicron was less evasive of the immunity created by vaccines, compared to immunity from natural infection in unvaccinated patients. This suggests that vaccination remains our best defense,” said Subramaniam.

作者指出，免疫逃逸的增加以及ACE2接口上强烈相互作用的保留，代表了重要的分子特征，可能有助于Omicron变体的快速扩散。

The increase in antibody evasion, the authors noted, “together with retention of strong interactions at the ACE2 interface, represent important molecular features that likely contribute to the rapid spread of the Omicron variant.”

根据观察到的结合亲和力和免疫逃逸的增加，研究人员表示，刺突蛋白突变可能是Omicron变体传播性增加的因素。

Based on the observed increase in binding affinity and antibody evasion, the researchers say that the spike protein mutations are likely contributing factors to the increased transmissibility of the Omicron variant.