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SARS-CoV-2 is heavily decorated by its surface Spike (S), a single-pass membrane protein that is key for the host-virus interactions. During the infection, S is cleaved by host proteases, yielding the N-terminal S1 and the C-terminal S2 subunit. S1 binds to angiotensin-converting enzyme 2 (ACE2) on the host cell membrane via its receptor-binding domain, causing conformational changes that trigger a secondary cleavage needed for the S2-mediated membrane fusion at the plasma membrane or in the endosome. Because of this essential role, RBD has been a hot spot for the development of therapeutic monoclonal antibodies (mAbs) and vaccine.