Understanding the Molecular Actions of Spike Glycoprotein in SARS-CoV-2 and Issues of a Novel Therapeutic Strategy for the COVID-19 Vaccine

In vaccine development, many use the spike protein (S protein), which has multiple “spike-like” structures protruding from the spherical structure of the coronavirus, as an antigen. However, there are concerns about its effectiveness and toxicity. When S protein is used in a vaccine, its ability to attack viruses may be weak, and its effectiveness in eliciting immunity will only last for a short period of time. Moreover, it may cause “antibody-dependent immune enhancement”, which can enhance infections. In addition, the three-dimensional (3D) structure of epitopes is essential for functional analysis and structure-based vaccine design. Additionally, during viral infection, large amounts of extracellular vesicles (EVs) are secreted from infected cells, which function as a communication network between cells and coordinate the response to infection. Under conditions where SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) molecular vaccination produces overwhelming SARS-CoV-2 spike glycoprotein, a significant proportion of the overproduced intracellular spike glycoprotein is transported via EVs. Therefore, it will be important to understand the infection mechanisms of SARA-CoV-2 via EV-dependent and EV-independent uptake into cells and to model the infection processes based on 3D structural features at interaction sites.