The COVID-19 pandemic is the result of infection with the SARS-CoV2 virus. The initial point of viral infection at the molecular level is mediated by the homo-trimeric Spike protein, a class I fusion protein embedded in the viral membrane. A single domain on the Spike known as the receptor binding domain (RBD) is responsible for interacting with the angiotensin-converting enzyme 2 (ACE2) receptor on the surface of human host-cells. Our laboratory is using a combined approach of high-resolution NMR spectroscopy and molecular dynamics and computational modeling to investigate the structure and dynamics that mediate the RBD-ACE2 interaction. The overall goal is to identify both binding and non-binding sub-states of the large and dynamic binding interface of the RBD, in order to 1) better understand the interaction between RBD and ACE2 and 2) provide potential templates for design of therapeutics that target the RBD.