论文标题

SARS-COV-2辐射诱导的疫苗开发的造成SARS-COV-2辐射诱导的灭活的蒙特卡洛模拟

Monte Carlo simulation of SARS-CoV-2 radiation-induced inactivation for vaccine development

论文作者

Francis, Ziad, Incerti, Sebastien, Zein, Sara A., Lampe, Nathanael, Guzman, Carlos A., Durante, Marco

论文摘要

灭活病毒免疫是目前正在测试开发SARS-COV-2疫苗的策略之一。用于灭活病毒的方法之一是暴露于高剂量的电离辐射以损害其核酸。尽管伽马射线有效地诱导了RNA病变,但包膜蛋白在此过程中也受到了高度损害。反过来,这可能会改变其抗原特性,影响其诱导能够提供有效保护的适应性免疫反应的能力。在这里,我们使用Monte Carlo Toolkit Geant4-DNA建模了稀疏和密集的电离辐射对SARS-COV-2的影响。使用现实的3D靶病毒模型,我们计算了峰值和膜蛋白以及病毒RNA中的预期病变数。我们表明,伽马射线会产生明显的尖峰蛋白损伤,但是密集的电离电荷颗粒会在相同水平的RNA病变中引起较少的膜损伤,因为通过核包膜的单个离子遍历足以使病毒失活。我们提出,加速带电的颗粒会产生灭活病毒,几乎没有结构损害包膜蛋白,从而代表了一种新的有效工具,用于开发针对SARS-COV-2和其他包膜病毒的疫苗。

Immunization with an inactivated virus is one of the strategies currently being tested towards developing a SARS-CoV-2 vaccine. One of the methods used to inactivate viruses is exposure to high doses of ionizing radiation to damage their nucleic acids. Although gamma-rays effectively induce lesions in the RNA, envelope proteins are also highly damaged in the process. This in turn may alter their antigenic properties, affecting their capacity to induce an adaptive immune response able to confer effective protection. Here, we modelled the impact of sparsely and densely ionizing radiation on SARS-CoV-2 using the Monte Carlo toolkit Geant4-DNA. With a realistic 3D target virus model, we calculated the expected number of lesions in the spike and membrane proteins, as well as in the viral RNA. We show that gamma-rays produce significant spike protein damage, but densely ionizing charged particles induce less membrane damage for the same level of RNA lesions, because a single ion traversal through the nuclear envelope is sufficient to inactivate the virus. We propose that accelerated charged particles produce inactivated viruses with little structural damage to envelope proteins, thereby representing a new and effective tool for developing vaccines against SARS-CoV-2 and other enveloped viruses.

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