Table 3.

Comparison of critical intermolecular interactions and binding affinity between the designed ACE2_24-83 peptides and SARS‐CoV‐2 RBD.

Interfacial Contacts	Hydrogen bonds										Electrostatic interactions		Hydrophobic interactions				ΔG (kcal/mol)	Kd (M)
SARS-CoV-2	N 487	K 417	Q 493	Y 505	Y 449	N 501	T 500	Q 498	Y 449	N 487	K 417	E 484	Y 489	F 486	F 486	F 486
Human ACE2	Q 24	D 30	E 35	E 37	D 38	Y 41	Y 41	Q 42	Q 42	Y 83	D 30	K 31	F 28	L 79	M 82	Y 83	−11.4	9.2E-09
rhesus macaque	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	−11.2	1.3E-08
hamster	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✕	✓	−11.5	8.2E-09
cat	✕	E	✓	✓	E	✓	✓	✓	✓	✓	E	✓	✓	✓	✕	✓	−11.3	1.1E-08
tiger	✕	E	✓	✓	E	✓	✓	✓	✓	✓	E	✓	✓	✓	✕	✓	−11.3	1.1E-08
ferret	✕	E	✓	✓	E	✓	✓	✓	✓	✓	E	✓	✓	✕	✕	✓	−11.7	6.0E-09
civet	✕	E	✓	✕	E	✓	✓	✓	✓	✓	E	✕	✓	✓	✕	✓	−11.9	4.4E-09
cattle	✓	E	✓	✓	✓	✓	✓	✓	✓	✓	E	✓	✓	M	✕	✓	−11.7	6.0E-09
sheep	✓	E	✓	✓	✓	✓	✓	✓	✓	✓	E	✓	✓	M	✕	✓	−11.9	4.1E-09
rabbit	✕	E	✓	✓	✓	✓	✓	✓	✓	✓	E	✓	✓	✓	✕	✓	−11.1	1.5E-08
dog	✕	E	✓	✓	E	✓	✓	✓	✓	✓	E	✓	✓	✓	✕	✓	−12.0	3.2E-09
pig	✕	E	✓	✓	✓	✓	✓	✓	✓	✓	E	✓	✓	I	✕	✓	−11.5	8.2E-09
pangolin	E	E	✓	✓	E	✓	✓	✓	✓	✓	E	✓	✓	I	✕	✓	−10.5	4.2E-08
bat	E	✓	✕	✓	✓	✕	✕	✓	✓	✓	✓	✓	✓	✓	✕	✓	−10.0	8.4E-08
mouse	N	N	✓	✓	✓	✓	✓	✓	✓	✕	✕	✕	✓	✕	✕	F	−10.7	3.0E-08
chicken	E	✕	✕	✓	✓	✓	✓	E	E	✕	✕	✕	✓	✕	✕	F	−10.7	2.9E-08
duck	✓	✕	✕	✓	✓	✓	✓	E	E	✕	✕	✕	✓	✕	✕	F	−11.0	1.6E-08

The green ticks and letters represent the presence of interactions, and the red crosses represent the absence of the interactions, respectively. ΔG and Kd value represent the binding free energy and the binding affinity, respectively.