New Mexico Consortium, Los Alamos, NM 87545, USA.
University of New Mexico, Albuquerque, NM 87131, USA.
Viruses. 2021 Jun 11;13(6):1126. doi: 10.3390/v13061126.
The SARS-CoV-2 virus has now become one of the greatest causes of infectious death and morbidity since the 1918 flu pandemic. Substantial and unprecedented progress has been made in the elucidation of the viral infection process in a short time; however, our understanding of the structure-function dynamics of the spike protein during the membrane fusion process and viral uptake remains incomplete. Employing computational approaches, we use full-length structural models of the SARS-CoV-2 spike protein integrating Cryo-EM images and biophysical properties, which fill the gaps in our understanding. We propose a membrane fusion model incorporating structural transitions associated with the proteolytic processing of the spike protein, which initiates and regulates a series of events to facilitate membrane fusion and viral genome uptake. The membrane fusion mechanism highlights the notable role of the S1 subunit and eventual mature spike protein uptake through the host membrane. Our comprehensive view accounts for distinct neutralizing antibody binding effects targeting the spike protein and the enhanced infectivity of the SARS-CoV-2 variant.
自 1918 年流感大流行以来，SARS-CoV-2 病毒现已成为导致传染性死亡和发病的最大原因之一。在短时间内，人们在阐明病毒感染过程方面取得了实质性的、前所未有的进展；然而，我们对刺突蛋白在膜融合过程和病毒摄取过程中的结构-功能动力学的理解仍不完整。我们采用计算方法，利用 Cryo-EM 图像和生物物理特性整合的全长 SARS-CoV-2 刺突蛋白结构模型，填补了我们理解上的空白。我们提出了一种膜融合模型，其中包含与刺突蛋白蛋白水解加工相关的结构转变，该转变启动并调节一系列事件，以促进膜融合和病毒基因组摄取。该膜融合机制突出了 S1 亚基的显著作用以及最终通过宿主膜摄取成熟的刺突蛋白。我们的综合观点解释了针对刺突蛋白的不同中和抗体结合效应以及 SARS-CoV-2 变体增强的感染性。
