Spike Glycoprotein and Host Cell Determinants of SARS-CoV-2 Entry and Cytopathic Effects
Hanh T. Nguyen, Shijian Zhang, Qian Wang, Saumya Anang, Jia Wang, Haitao Ding, John C. Kappes, Joseph Sodroski
Abstract
The development of an effective and durable SARS-CoV-2 vaccine is essential for combating the growing COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein is the main target of neutralizing antibodies elicited during virus infection or following vaccination. Knowledge of the spike glycoprotein evolution, function and interactions with host factors will help researchers to develop effective vaccine immunogens and treatments. Here we identify key features of the spike glycoprotein, including the furin cleavage site and the D614G natural mutation, that modulate viral cytopathic effects, infectivity and sensitivity to inhibition. We also identify two inhibitors of host metalloproteases that block S-mediated cell-cell fusion, a process that contributes to the destruction of the virus-infected cell.