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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒真实三维形状的重建。

Reconstruction of the real 3D shape of the SARS-CoV-2 virus.

作者信息

Balabdaoui Fadoua, Wierzbicki Tomasz, Bao Emma

机构信息

Seminar für Statistik, Zürich, Switzerland.

Department of Mechanical Engineering, MIT, Cambridge, Massachusetts.

出版信息

Biophys J. 2024 May 21;123(10):1297-1310. doi: 10.1016/j.bpj.2024.04.019. Epub 2024 May 6.

Abstract

The photographs of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus taken by electron transmission microscopy and cryoelectron microscopy provide only a 2D silhouette. The viruses appear to look like distorted circles. The present paper questions the real shape of the SARS-CoV-2 virus and makes an attempt to give an answer. Is this a general ellipsoid, a spheroid with rotational symmetry, a sphere, or something else? The answer requires the application of tools from three different disciplines: structural mechanics, microbiology, and statistics. A total of 590 virus photographs taken from 22 recently published papers were examined. From this experimental data pool, the histogram of diameter ratios was built from the 283 measurements where the virus images could be approximated as ellipses. The curve peaks at the diameter ratio of 1.22. The transformation equation for the spatial shape to the planar shade was derived for a fixed light source of the microscope. This equation involves an unknown orientation of the viruses with respect to the microscope. Two sets of models were developed, one with a uniform distribution of the virus orientation and the other with the orientation defined by the normalized beta distribution. In both sets of models, the unknown diameter ratio of the spheroidal virus was regarded as a random realization from translated gamma distributions. The parameters of the distribution of the kernel functions were determined by minimizing the mean square difference between the predicted and measured 2D histograms. The information included in the measured histograms was found to be insufficient to find an unknown distribution of the virus's orientation. Simply too many unknown parameters render the solution physically unrealistic. The minimization procedure with a uniform probability of virus orientation predicted the peak of the aspect ratio of the 3D spheroid at 1.32. Based on this result, models of the virus will be developed in the continuation of this research for a full dynamic analysis.

摘要

通过电子透射显微镜和冷冻电子显微镜拍摄的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒的照片仅提供了二维轮廓。这些病毒看起来像是变形的圆圈。本文对SARS-CoV-2病毒的真实形状提出质疑,并试图给出答案。它是一般的椭球体、具有旋转对称性的球体、球体,还是其他形状?答案需要应用来自三个不同学科的工具:结构力学、微生物学和统计学。我们检查了从最近发表的22篇论文中获取的总共590张病毒照片。从这个实验数据池中,根据283次测量构建了直径比直方图,在这些测量中病毒图像可以近似为椭圆。曲线在直径比为1.22处达到峰值。针对显微镜的固定光源,推导了空间形状到平面阴影的变换方程。该方程涉及病毒相对于显微镜的未知方向。开发了两组模型,一组病毒方向分布均匀,另一组方向由归一化贝塔分布定义。在这两组模型中,将椭球形病毒的未知直径比视为平移伽马分布的随机实现。通过最小化预测的和测量的二维直方图之间的均方差来确定核函数分布的参数。发现测量直方图中包含的信息不足以找到病毒方向的未知分布。仅仅太多的未知参数使得解决方案在物理上不现实。具有均匀病毒方向概率的最小化程序预测三维球体的纵横比峰值为1.32。基于这一结果,将在本研究的后续中开发病毒模型以进行完整的动态分析。

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