. 2021 Mar 30;133:104359. doi: 10.1016/j.compbiomed.2021.104359

Table 3.

Virtual screening (obtained by AutoDock VINA), molecular docking (obtained by AutoDock 4.2.6) results and ROC probability of compounds binding to spike protein. Top 10 compounds are shown, each from FDA-approved drugs, natural compounds taken from literature and ZINC database. Binding affinities are expressed as lowest binding energies (LBE) in kcal/mol obtained. The ROC probabilities are based on the model obtained from positive and negative control drugs. Those compounds are labeled in bold, where VINA and AutoDock revealed binding energies < −7 kcal/mol. Amino acid residues forming hydrogen bonds are labeled in bold.

Dataset	ROC probability	VINA defined	AutoDock defined	Interacting amino acid residues
Dataset	ROC probability	LBE	LBE	Interacting amino acid residues
FDA-approved drugs:
Simeprevir	0.993	−8.73 ± 0.06	−10.09 ± 0.10	Asn334, Leu335, Cys336, Pro337, Phe338, Gly339, Phe342, Asn343, Cys361, Asp364, Val367, Leu368, Phe374
Paritaprevir	0.997	−9.27 ± 0.15	−10.04 ± 0.06	Tyr449, Leu452, Leu455, Phe456, Glu484, Tyr489, Phe490, Leu492, Gln493, Ser494, Tyr495, Gly496
Velpatasvir	0.999	−8.57 ± 0.12	−9.11 ± 0.09	Leu335, Phe338, Gly339, Phe342, Asn343, Val362, Asp364, Val367, Leu368, Ser371, Ser373, Phe374, Pro527, Lys528
Rifapentine	0.998	−8.80 ± 0.17	−8.84 ± 0.03	Arg355, Gly381, Val382, Phe392, Tyr396, Phe429, Thr430, Phe464, Ser514, Phe515, Glu516, Leu517, Leu518
Eribulin	0.999	−8.43 ± 0.15	−8.82 ± 0.08	Phe456, Glu484, Gly485, Phe486, Tyr489, Phe490
Teniposide	0.997	−8.63 ± 0.06	−8.46 ± 0.08	Leu335, Phe338, Gly339, Phe342, Asn343, Asp364, Leu368, Phe374, Trp436, Leu441
Trabectedin	0.995	−8.11 ± 0.10	−7.91 ± 0.04	Leu335, Cys336, Pro337, Phe338, Gly339, Phe342, Asn343, Ala363, Asp364, Val367, Ser371, Ser373, Phe374
Ivermectin	0.999	−9.07 ± 0.06	−7.49 ± 0.04	Trp353, Arg355, Tyr396, Asp428, Phe429, Thr430, Lys462, Pro463, Phe464, Glu465, Glu516
Ledipasvir	0.999	−8.53 ± 0.15	−7.31 ± 0.09	Tyr449, Leu452, Glu484, Gly485, Cys488, Phe490, Leu492, Gln493, Ser494
Nystatin	0.994	−8.53 ± 0.15	−6.83 ± 0.07	Pro426, Asp427, Asp428, Arg457, Ser459, Lys462, Pro463, Glu465, Arg466
Natural compounds from literature:
Euphol	1.000	−7.93 ± 0.06	−9.13 ± 0.10	Arg454, Arg457, Lys458, Asp467, Ser469, Tyr473, Gln474, Ala475
Loniflavone	0.996	−9.23 ± 0.12	−8.59 ± 0.03	Leu335, Cys336, Phe338, Val362, Ala363, Asp364, Val367, Leu368, Ser371, Ser373, Phe374, Trp436, Asn437, Ser438, Asn440, Leu441
Amyrin	0.996	−9.03 ± 0.06	−8.46 ± 0.03	Arg355, Pro426, Asp428, Thr430, Phe464, Ser514, Phe515, Glu516
Procyanidin	0.999	−8.77 ± 0.15	−7.37 ± 0.02	Tyr396, Pro426, Asp428, Phe429, Thr430, Pro463, Phe464, Ser514, Phe515, Glu516, Leu517
Crinine	0.999	−7.77 ± 0.06	−6.84 ± 0.08	Arg454, Arg457, Lys458, Ser459, Ser469, Glu471, Tyr473, Pro491
Quercetin	0.993	−7.87 ± 0.06	−6.77 ± 0.09	Asp467, Ser469, Glu471, Tyr473, Gln474, Ala475, Pro491
IlexsaponinB2	1.000	−8.43 ± 0.06	−6.70 ± 0.15	Ala372, Tyr369, Ser375, Cys379, Tyr380, Gly381, Phe344
Strictinin	0.998	−7.83 ± 0.12	−6.26 ± 0.07	Arg454, Phe456, Lys458, Arg466, Asp467, Ile468, Ser469, Ile472, Tyr473
Quercetin-3-o-rutinoside	0.999	−8.23 ± 0.05	−5.12 ± 0.11	Cys480, Agr454, Phe456, Lys458, Gly471, Ile472, Tyr473, Gln474
Punicalagin	1.000	−8.11 ± 0.11	−4.22 ± 0.07	Phe377, Lys378, Cys379, Tyr380, Gly381, Val382, Ser383, Pro384, Arg408
Natural compounds from ZINC database:
ZINC000252515584; (1R,3S,6S,7E,13S,16R,17R,21S,22S)-28-Hydroxy-17-[(2R,4R,5S,6R)-4-hydroxy-5-[(2S,4R,5R,6R)-5-hydroxy-4-(2-methoxy-6-methylbenzoyl)oxy-6-methyloxan-2-yl]oxy-6-methyloxan-2-yl]oxy-3,22-dimethyl-23,26-dioxo-24,27-dioxapentacyclo [23.2.1.01,6.013,22.016,21]octacosa-4,7,14,25 (28)-tetraene-4-carboxylic acid	0.999	−9.57 ± 0.09	−10.21 ± 0.08	Trp353, Asn354, Arg355, Pro426, Asp428, Thr430, Pro463, Phe464, Glu465, Arg466, Ser514
ZINC000027215482; (1R,4S,7S)-4-benzyl-9-[(1R,4S,7R)-4-benzyl-3,6-dioxo-2,5,16-triazatetracyclo [7.7.0.0²,⁷.0¹⁰,¹⁵]hexadeca-10,12,14-trien-9-yl]-2,5,16-triazatetracyclo [7.7.0.0²,⁷.0¹⁰,¹⁵]hexadeca-10 (15),11,13-triene-3,6-dione	0.997	−9.83 ± 0.06	−9.64 ± 0.09	Arg457, Lys458, Ser459, Asn460, Lys462, Ser469, Tyr473, Gln474, Gly476
ZINC000027215486; (1R,4S,7S)-4-benzyl-9-[(1R,4S,7S)-4-benzyl-3,6-dioxo-2,5,16-triazatetracyclo [7.7.0.0²,⁷.0¹⁰,¹⁵]hexadeca-10,12,14-trien-9-yl]-2,5,16-triazatetracyclo [7.7.0.0²,⁷.0¹⁰,¹⁵]hexadeca-10 (15),11,13-triene-3,6-dione	0.997	−9.38 ± 0.07	−8.82 ± 0.11	Phe342, Asn343, Ala344, Thr345, Ser371, Ser373, Phe374, Trp436, Asn440, Arg509
ZINC000095788030; 5-[(1R,3aS,3bR,7S,9aR,11aR)-7-{[(2R,3R,4R,5S,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-{[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy}oxan-2-yl]oxy}-3a-hydroxy-9a,11a-dimethyl-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta [a]phenanthren-1-yl]-2H-pyran-2-one	0.993	−9.08 ± 0.08	−8.13 ± 0.10	Phe338, Gly339, Phe342, Asn343, Ala344, Asp364, Val367, Leu368, Ser371, Ser373, Phe374, Trp436, Arg509
ZINC000150343123	0.999	−8.70 ± 0.10	−7.82 ± 0.07	Arg454, Phe456, Arg457, Lys458, Ser469, Glu471, Ile472, Tyr473, Gln474, Pro479, Cys480, Asn481, Pro491
ZINC000255205550; (4aS,6aS,6bR,10S,12aR,14bS)-10-{[(2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-({[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}methyl)oxan-2-yl]oxy}-2,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylic acid	0.998	−8.93 ± 0.06	−7.64 ± 0.07	Trp353, Arg355, Tyr396, Asp428, Phe429, Thr430, Phe464, Arg466, Ser514
ZINC000514287935; 6-[1-(9a,11a-dimethyl-9-oxo-7-)[3,4,5-trihydroxy-6-()[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy)methyl)oxan-2-yl]oxy)-1H,2H,3H,3aH,3bH,4H,6H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta [a]phenanthren-1-yl)-1-hydroxyethyl]-3,4-dimethyl-5,6-dihydro-2H-pyran-2-one	0.999	−8.85 ± 0.05	−7.12 ± 0.09	Arg355, Tyr396, Asp428, Phe429, Thr430, Arg457, Pro463, Phe464, Glu465, Arg466, Asp467, Ile468, Ser514, Phe515
ZINC000253500823; 15'-[(5-{[3,4-dihydroxy-6-(hydroxymethyl)-5-{[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}oxan-2-yl]oxy}-3-hydroxy-4-methoxy-6-methyloxan-2-yl)oxy]-7′-hydroxy-8′,12′-dimethyl-6′-oxaspiro [oxolane-3,5′-pentacyclo [9.8.0.0¹,⁷.0⁴,⁸.0¹²,¹⁷]nonadecan]-5-one	0.999	−9.06 ± 0.10	−6.93 ± 0.06	Leu335, Phe338, Gly339, Phe342, Asn343, Asp364, Val367, Leu368, Ser371, Ser373, Phe374, Trp436, Asn440, Leu441
ZINC000253389471; (4aR,5R,6aS,6bR,10S,12aR)-10-{[(2R,3R,4R,5S,6R)-6-({[(2S,3R,4S,5S)-4,5-dihydroxy-3-{[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxy}oxan-2-yl]oxy}methyl)-3-acetamido-4,5-dihydroxyoxan-2-yl]oxy}-5-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylic acid	0.999	−9.20 ± 0.10	−6.22 ± 0.12	Leu368, Tyr369, Ser371, Ala372, Phe374, Ser375, Phe377, Lys378, Cys379, Tyr380, Pro384
ZINC000253500685; 4-[(7S,9aS,11aR)-3a-hydroxy-7-[(4-methoxy-6-methyl-5-{[3,4,5-trihydroxy-6-({[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}methyl)oxan-2-yl]oxy}oxan-2-yl)oxy]-9a,11a-dimethyl-hexadecahydro-1H-cyclopenta [a]phenanthren-1-yl]-2,5-dihydrofuran-2-one	0.995	−9.67 ± 0.06	−5.94 ± 0.16	Gly381, Pro426, Asp428, Thr430, Ser514, Phe515, Glu516, Leu517