  SARS-CoV-2 is what has caused the COVID-19 pandemic. Early viral infection is
mediated by the SARS-CoV-2 homo-trimeric Spike (S) protein with its receptor
binding domains (RBDs) in the receptor-accessible state. We performed molecular
dynamics simulation on the S protein with a focus on the function of its
N-terminal domains (NTDs). Our study reveals that the NTD acts as a "wedge" and
plays a crucial regulatory role in the conformational changes of the S protein.
The complete RBD structural transition is allowed only when the neighboring NTD
that typically prohibits the RBD's movements as a wedge detaches and swings
away. Based on this NTD "wedge" model, we propose that the NTD-RBD interface
should be a potential drug target.
