Hu Yiwen, Buehler Markus J
Laboratory for Atomistic and Molecular Mechanics (LAMM), Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Matter. 2021 Jan 6;4(1):265-275. doi: 10.1016/j.matt.2020.10.032. Epub 2020 Nov 2.
The novel coronavirus disease 2019 (COVID-19) has spread rapidly around the world. Its causative virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), enters human cells through the physical interaction between the receptor-binding domain (RBD) of its spike protein and the human cell receptor ACE2. Here, we provide a novel way of understanding coronavirus spike proteins, connecting their nanomechanical features, specifically their vibrational spectrum and quantitative measures of mobility, with virus lethality and infection rate. The key result of our work is that both the overall flexibility of upward RBD and the mobility ratio of RBDs in different conformations represent two significant factors that show a positive scaling with virus lethality and an inverse correlation with the infection rate. Our analysis shows that epidemiological virus properties can be linked directly to pure nanomechanical, vibrational aspects, offering an alternative way of screening new viruses and mutations, and potentially exploring novel ways to prevent infections from occurring.
2019年新型冠状病毒病(COVID-19)已在全球迅速传播。其致病病毒,即严重急性呼吸综合征冠状病毒2(SARS-CoV-2),通过其刺突蛋白的受体结合域(RBD)与人类细胞受体ACE2之间的物理相互作用进入人体细胞。在此,我们提供了一种理解冠状病毒刺突蛋白的新方法,将其纳米力学特征,特别是其振动光谱和迁移率的定量测量,与病毒致死率和感染率联系起来。我们工作的关键结果是,向上RBD的整体柔韧性以及不同构象下RBD的迁移率比值均代表两个重要因素,它们与病毒致死率呈正相关,与感染率呈负相关。我们的分析表明,流行病学病毒特性可直接与纯纳米力学振动方面相关联,为筛选新病毒和突变提供了一种替代方法,并有可能探索预防感染发生的新途径。