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. 2021 Mar 21;26(6):1754. doi: 10.3390/molecules26061754

Table 2.

Anti-Human Coronavirus (Anti-HCoV) activities of natural compounds.

No. Mode of Action IC50 (μM) CC50 (μM) EC50 (μM) SI Concentration (μM) Positive Control Ref.
Alkaloids
7 Inhibition of SARS-CoV (BJ-001 strain) - 14,980.0 ± 912.0 a 15.7 ± 1.2 a 954 - Interferon alpha, CC50 > 100,000 ± 710.1 μM, EC50 = 660.3 ± 119.1 μM, SI > 151 [23]
8 Inhibition of HCoV-OC43 infected MRC-5 human lung cells 0.33 ± 0.03 13.41 ± 0.36 - 40.19 2–20 - [30]
9 1.01 ± 0.07 11.54 ± 0.46 - 11.46
10 0.83 ± 0.07 11.26 ± 0.69 - 13.63
11 Inhibition of SARS-CoV replication - 25 3.4 7.3 - - [31]
Anthraquinones
18 Blocks the interaction of SARS spike protein to ACE-2 200 - - - 0.1–400 Promazine [32]
Flavonoids and flavonoid glycosides
19 Inhibition of SARS-CoV 3CL Protease 8.3 (2.5 ± 0.8 μg/mL) 2718 (820 ± 15 μg/mL) - - - - [47]
22 Inhibition of wild-type SARS-CoV infection - 155 10.6 (9.2–12.2) 14.62 0.1–10,000 Glycyrrhizin (111), EC50 > 607.6 μM;
Ribavirin, not effect		 [44,50]
23 Inhibition of entry of HIV-luc/SARS pseudotypeed virus into Vero E6 cells - 3320 83.4 39.81 0.1–10,000 - [60]
24 Inhibition of SARS-CoV helicase, nsP13 2.71 ± 0.19 - - - 0.01–10 [51]
25 0.86 ± 0.48 - - -
31 Inhibition of SARS-CoV 3CL Protease 33.17 - - - 2–320 - [57]
32 27.45 - - -
33 37.78 - - -
36 Inhibition of SARS-CoV 3CL Protease 42.79 ± 4.97 - - - 9.4–80 - [58]
38 24.14 ± 4.32 - - -
39 31.62 ± 2.43 - - -
40 48.85 ± 8.15 - - -
41 61.46 ± 9.13 - - -
36 Inhibition of SARS-CoV 3CL Protease Q189A 127.89 ± 10.06 - - - 16.5–200
45 Inhibition of SARS-CoV papain-like protease 6.2 ± 0.04 - - - 0.1–100 - [34]
46 6.1 ± 0.02 - - -
47 11.6 ± 0.13 - - -
48 12.5 ± 0.22 - - -
49 5.0 ± 0.06 - - -
50 9.5 ± 0.10 - - -
51 9.2 ± 0.13 - - -
52 13.2 ± 0.14 - - -
53 12.7 ± 0.19 - - -
54 14.4 ± 0.27 - - -
55 10.4 ± 0.16 - - -
56 13.9 ± 0.18 - - -
64 Inhibition of SARS-CoV 3CL Protease 280.8 ± 21.4 - - - 1–1000 Luteolin (22), IC50 = 20.0 ± 2.2 μM;
Quercetin (23), IC50 = 23.8 ± 1.9 μM		 [35]
65 8.3 ± 1.2 - - -
66 72.3 ± 4.5 - - -
67 32.0 ± 1.7 - - -
68 34.8 ± 0.2 - - -
Lignans and neolignans
69 Inhibition of Vero E6 cell proliferation and SARS-CoV replication - >750 >10 N.C. b 0.01–10 Niclosamide, CC50 = 22.1 μM, EC50 < 0.1 μM, SI > 221;
Valinomycin, CC50 = 67.5 μM, EC50 = 1.63 μM, SI = 41.4		 [36]
70 - >750 1.13 >667
72 - 88.9 6.50 13.7
73 - 68.3 3.80 18.0
69 Inhibition of SARS-CoV 3CL Protease >100 - - - 8–80 Niclosamide, IC50 = 40 μM
70 25 - - -
Gallic acid derivatives
74 Inhibition of wild-type SARS-CoV infection - 1.08 4.5 (1.96–5.8) 240 0.1–10,000 Glycyrrhizin (111), EC50 > 607.6 μM;
Ribavirin, not effect		 [60]
75 Inhibition of SARS-CoV 3CL Protease 3 - - - 4–20 N-Ethylmaleimide [61]
76 43 - - -
77 9.5 - - -
Sesquiterpenoids
84 Inhibition of Vero E6 cell proliferation and SARS-CoV replication - >750 >10 N.C. b 0.01–10 Niclosamide, CC50 = 22.1 μM, EC50 < 0.1 μM, SI > 221;
Valinomycin, CC50 = 67.5 μM, EC50 = 1.63 μM, SI = 41.4		 [36]
85 - 76.8 4.44 17.3
Diterpenoids
87 Inhibition of Vero E6 cell proliferation and SARS-CoV replication - 80.4 1.39 58.0 0.01–10 Niclosamide, CC50 = 22.1 μM, EC50 < 0.1 μM, SI > 221;
Valinomycin, CC50 = 67.5 μM, EC50 = 1.63 μM, SI = 41.4		 [36]
88 - 305.1 4.00 76.3
90 - 78.5 >10 <7.9
91 - >750 1.47 >510
92 - 127 1.15 111
93 - 89.7 5.55 16.2
94 - 303.3 1.57 193
95 - >750 4.71 >159
96 - 674 7.5 89.8
87 Inhibition of SARS-CoV 3CL Protease 49.6 ± 1.5 - - - 0.1–1000 Abietic acid (104), IC50 = 189.1 ± 15.5 μM [35]
97 220.8 ± 10.4 - - -
98 233.4 ± 22.2 - - -
99 163.2 ± 13.8 - - -
100 128.9 ± 25.2 - - -
101 207.0 ± 14.3 - - -
102 283.5 ± 18.4 - - -
103 137.7 ± 12.5 - - -
Triterpenoids
105 Inhibition of Vero E6 cell proliferation and SARS-CoV replication - 150 >10 <15 - Niclosamide, CC50 = 22.1 μM, EC50 < 0.1 μM, SI > 221;
Valinomycin, CC50 = 67.5 μM, EC50 = 1.63 μM, SI = 41.4		 [36]
106 - 112 0.63 180
105 Inhibition of SARS-CoV 3CL Protease 10 - - - 8–80 Niclosamide, IC50 = 40 μM
106 >100 - - -
Saponins
111 - >20,000 * 300 (51) * >67 - - [40]
112 Inhibition of SARS-CoV replication - >3000 40 ± 13 >75 0.1–1000 Glycyrrhizin (111), CC50 > 24,000 μM, EC50 = 365. ± 12 μM, SI > 65 [63]
113 - 1462 ± 50 35 ± 7 41
114 - 215 ± 18 139 ± 20 2
120 - 44 ± 6 8 ± 2 6
121 - 250 ± 19 50 ± 10 5
122 - 15 ± 3 5 ± 3 3
123 - 66 ± 8 16 ± 1 4
127 Inhibition of HCoV-OC43 infected MRC-5 human lung cells - 228.1 ± 3.8 8.6 ± 0.3 26.6 0.25–25 Actinomycin D, CC50 = 2.8 ± 0.3 μM, EC50 = 0.02 ± 0.0 μM, SI = 140 [64]
128 - 383.3 ± 0.2 1.7 ± 0.1 ** 221.9
129 - 121.5 ± 0.1 19.9 ± 0.1 *† 19.2
130 - 176.2 ± 0.2 13.2 ± 0.3 *†‡ 13.3
131 Inhibition of SARS-CoV replication - 15.0 6.0 2.5 - - [30]

a nm; b not calculable; * mg/L; ** p < 0.05 compared with saikosaponin A; *† p < 0.05 compared with saikosaponin B2; *†‡ p < 0.05 compared with saikosaponin C (student’s test).