Table 1.

Characteristics of the 35 top ligands of 3CL^proidentified by MD simulations. The compounds selected for validation in a 3CL^pro inhibition assay are highlighted in bold.

No.	Compound name	Class	ddyad [Å]	dBS [Å]	$\mathrm{\Delta }{G}_{\mathrm{bind}}$ [kcal/mol]
Interaction with both catalytic dyad residues (H41 and C145)
1	Cilostazol	FDA	$\mathbf{2}.\mathbf{295}$	$\mathbf{1}.\mathbf{856}$	$-\mathbf{49}.\mathbf{9}\pm \mathbf{4}.\mathbf{8}$
2	Proanthocyanidin A1	NP	$2.151$	$1.696$	$-45.4\pm 5.9$
3	Rhoifolin	NP	$\mathbf{2}.\mathbf{101}$	$\mathbf{1}.\mathbf{745}$	$-\mathbf{44}.\mathbf{1}\pm \mathbf{7}.\mathbf{4}$
4	Apixaban	FDA	$\mathbf{2}.\mathbf{511}$	$\mathbf{1}.\mathbf{901}$	$-\mathbf{43}.\mathbf{4}\pm \mathbf{5}.\mathbf{2}$
5	Theacitrin C	NP	$2.278$	$1.660$	$-42.9\pm 7.1$
6	Corilagin	NP	$\mathbf{2}.\mathbf{134}$	$\mathbf{1}.\mathbf{667}$	$-\mathbf{41}.\mathbf{5}\pm \mathbf{5}.\mathbf{1}$
7	Dihydroergotoxine	non-FDA	$\mathbf{2}.\mathbf{456}$	$\mathbf{1}.\mathbf{810}$	$-\mathbf{40}.\mathbf{8}\pm \mathbf{5}.\mathbf{8}$
8	Telcagepant	INV	$\mathbf{2}.\mathbf{665}$	$\mathbf{1}.\mathbf{931}$	$-\mathbf{39}.\mathbf{1}\pm \mathbf{4}.\mathbf{0}$
9	ZINC000002114470	NP	$2.479$	$1.817$	$-37.3\pm 5.6$
10	ZINC000011865175	NP	$\mathbf{2}.\mathbf{046}$	$\mathbf{2}.\mathbf{012}$	$-\mathbf{36}.\mathbf{7}\pm \mathbf{3}.\mathbf{5}$
11	Lurasidone	FDA	$\mathbf{2}.\mathbf{153}$	$\mathbf{1}.\mathbf{963}$	$-\mathbf{35}.\mathbf{6}\pm \mathbf{3}.\mathbf{4}$
12	ZINC000049888572	INV	$2.109$	$1.930$	$-33.5\pm 5.1$
13	Hypericin	INV	$\mathbf{2}.\mathbf{410}$	$\mathbf{1}.\mathbf{865}$	$-\mathbf{31}.\mathbf{8}\pm \mathbf{3}.\mathbf{8}$
14	Pimozide	FDA	$2.382$	$1.928$	$-30.6\pm 3.5$
15	Sotrastaurin	INV	$2.143$	$1.911$	$-29.9\pm 3.6$
16	Proanthocyanidin A2	NP	$\mathbf{2}.\mathbf{584}$	$\mathbf{1}.\mathbf{845}$	$-\mathbf{29}.\mathbf{0}\pm \mathbf{5}.\mathbf{4}$
17	Enzastaurin	INV	$2.545$	$1.910$	$-27.3\pm 4.0$
18	ZINC000008297065	NP	$2.030$	$1.992$	$-27.0\pm 4.4$
19	Telmisartan	FDA	$2.360$	$1.908$	$-4.2\pm 6.1$
Interaction with one catalytic dyad residues (H41 or C145)
20	Isocorilagin	NP	$2.250$	$1.683$	$-42.4\pm 6.0$
21	Dasatinib	FDA	$\mathbf{2}.\mathbf{361}$	$\mathbf{1}.\mathbf{881}$	$-\mathbf{37}.\mathbf{4}\pm \mathbf{5}.\mathbf{4}$
22	Teniposide	FDA	$\mathbf{2}.\mathbf{232}$	$\mathbf{1}.\mathbf{796}$	$-\mathbf{36}.\mathbf{2}\pm \mathbf{6}.\mathbf{4}$
23	Palbociclib	FDA	$\mathbf{2}.\mathbf{347}$	$\mathbf{1}.\mathbf{942}$	$-\mathbf{35}.\mathbf{6}\pm \mathbf{3}.\mathbf{4}$
24	Tadalafil	FDA	$2.333$	$1.938$	$-33.9\pm 3.2$
25	ZINC000012881832	NP	$2.153$	$1.984$	$-33.5\pm 6.0$
26	TMC647055	INV	$2.336$	$2.083$	$-31.8\pm 4.9$
27	Fenoverine	INV	$2.281$	$2.005$	$-31.5\pm 3.3$
28	Zeylanone	NP	$2.827$	$1.954$	$-29.5\pm 3.7$
29	Remdesivir	NP	$2.421$	$1.843$	$-29.0\pm 5.4$
30	Estradiol	ST	$\mathbf{2}.\mathbf{395}$	$\mathbf{1}.\mathbf{880}$	$-\mathbf{26}.\mathbf{5}\pm \mathbf{3}.\mathbf{9}$
31	Disulfiram	REF	$2.317$	$2.102$	$-24.1\pm 2.8$
32	Epitaraxerol	NP	$2.263$	$2.049$	$-23.7\pm 3.1$
33	Theaflavin	NP	$2.482$	$1.847$	$-23.5\pm 4.9$
34	Daidzein	NP	$2.504$	$1.760$	$-22.9\pm 3.5$
35	Montelukast	FDA	$2.186$	$1.896$	$-12.6\pm 7.5$