<p>The spike
glycoprotein (S-protein) mediates SARS-CoV-2 entry via intermolecular interaction
with human angiotensin-converting enzyme 2 (hACE2). The receptor-binding domain
(RBD) of the S-protein has been considered critical for this interaction and
acts as the target of numerous neutralizing antibodies and antiviral peptides.
This study used the fragment molecular orbital (FMO) method to analyze the
interactions between RBD and antibodies/peptides and extracted crucial residues
that can be used to epitopes. The interactions evaluated as inter-fragment interaction energy
(IFIE) values between the RBD and 12 antibodies/peptides showed a fairly good correlation
with the experimental activity pIC<sub>50</sub> (<i>R</i><sup>2</sup> = 0.540). Nine residues (T415, K417, Y421, F456,
A475, F486, N487, N501, and Y505) were confirmed as crucial. Pair interaction energy
decomposition analyses (PIEDA) showed that hydrogen bonds,
electrostatic interactions, and π-orbital interactions are important. Our
results provide essential information for understanding
SARS-CoV-2-antibodies/peptide binding and may play roles in future antibody/antiviral
drug design. </p>