SARS-CoV-2 spike behavior in situ: a Cryo-EM images for a better understanding of the COVID-19 pandemic
Alaa M. Ismail, Abdo A. Elfiky
Abstract
Most recently in Nature Journal, Ke et al. thoroughly investigate the SARS-CoV-2 spike in situ by using cryo-electron microscopy (Cryo-EM) to reveal its different conformations, orientations, and distribution over the virion particles. he cornerstone of any viral infection is the recognition of the viral element, usually a glycoprotein, to the host cell receptors. Knowledge of the behavior of viral glycoprotein is crucial for understanding the mode of infection and designing a vaccine against viruses. The spike glycoprotein is the critical viral element that is responsible for host cell recognition, attachment, and entry for the human coronaviruses. The trimeric spikes are the transmembrane protein that undergoes dramatic structural rearrangements for binding to its host cell receptor, the angiotensin-converting enzyme 2 (ACE2), that mediate subsequent membrane fusion and virion entry. Drug designers and vaccine developers are intriguingly studying the spike glycoprotein of SARS-CoV-2 due to its paramount importance in viral-host cell communications. The spike glycoprotein was the first SARS-CoV-2 protein to be solved experimentally (6VSB), released on the Protein Data Bank on February 26, 2020. Due to the colossal structure of the trimeric spike (1300 residues per monomer), Cryo-EM was utilized to get the 3D structures of the different states of the trimeric spike glycoprotein. e et al. infected VeroE6 and the lung cancer Calu-3 cells with SARS-CoV-2 then imaged the fixed supernatant with Cryo-EM. The virions are slightly larger in diameter in the case of Calu-3 cells (104 13 nm) compared to the VeroE6 cells (91 11 nm). In both systems, the trimeric spike takes two main isoforms, the prefusion (97%) and the postfusion (3%), as shown in Fig.