Binding scores, RMSD values, and amino acid interactions of the tested compounds (1–6), into the binding sites of SARS-CoV-2 spike (S) and main protease (Mpro).

Compound	Pocket	Scorea	RMSD_refineb	Interactions	Distance Å
1	S	−5.80	1.04	His195/pi-H	3.60
	Mpro	−6.67	1.75	Cys145/H-acceptor	3.02
				His163/H-acceptor	3.22
				Asn142/pi-H	3.81
				Asn142/pi-H	4.54
2	S	−6.12	1.18	Asn194/H-donor	3.07
				Asn194/H-donor	3.52
	Mpro	−6.11	1.45	Cys145/H-acceptor	3.13
				Met165/H-acceptor	3.30
				Asn142/pi-H	4.14
3	S	−6.16	1.29	Gln86/H-donor	3.02
				Gln81/H-donor	3.34
	Mpro	−6.63	1.44	Glu166/H-acceptor	3.06
				Met165/H-donor	4.02
				Asn142/pi-H	4.09
				Gln189/pi-H	4.18
4	S	−7.85	1.69	Gln101/H-donor	2.75
				Gln98/H-donor	2.95
				Asn103/H-donor	3.01
				Asn194/H-donor	3.22
	Mpro	−9.23	2.19	His163/H-acceptor	3.05
				Glu166/H-donor	3.39
5	S	−5.73	0.85	Gln81/H-donor	2.96
				Glu81/pi-H	3.81
				Gln102/pi-H	4.07
				Gln101/pi-H	4.50
	Mpro	−5.83	1.07	Leu141/H-donor	2.81
				Glu166/H-acceptor	3.24
6	S	−6.90	2.14	Gln81/H-donor	2.96
	Mpro	−6.77	1.59	Ser46/H-acceptor	2.84
				Glu166/H-acceptor	2.98
N3, 7	Mpro	−10.70	2.30	Leu141/H-donor	2.85
				Gln189/H-donor	2.87
				Thr190/H-donor	3.04
				Glu166/H-acceptor	3.10
				Glu166/H-donor	3.15
				His163/H-acceptor	3.43
				His164/H-donor	3.54
				Thr25/pi-H	4.09
				Thr26/pi-H	4.15

^aS: score of a compound inside the protein binding pocket (kcal mol⁻¹).

^bRMSD_refine: root mean squared deviation after and before refinement between the predicted pose and the crystal structure, respectively.