Table 1.

Anticoronavirus actions of natural phenolic compounds.

Compound	Mechanism of Action	IC50	CC50	SI	Experimental Model	Reference
Quercetin	-	198.5 μM	-	-	HCoV-OC43 and NCDCV infection of embryonic bovine lung fibroblasts	[20]
Apigenin, Luteolin, and Catechin	Blockade of early steps of viral life cycle	Apigenin: 0.37–0.74 μM Luteolin: 0.7–1.4 μM Catechin: 37.9–41.3 μM	Apigenin: >185 μM Luteolin: 23.4 μM Catechin: >341.7 μM	Apigenin: 250–500 Luteolin: 16.75–33.5 Catechin: 8.3–9	PEDV infection of Vero cells and Sulforhodamine B assay for cytotoxicity	[21]
Luteolin and Quercetin	Inhibiton of viral entry by binding to S2 domain of S protein and inhibiting fusion	Luteolin: 10.6 μM Quercetin: 83.4 μM	Luteolin: 155 μM Quercetin: 3320 μM	Luteolin: 14.62 Quercetin: 39.8	SARS-CoV live virus and HIV-luc/SARS pseudotyped viral infection of Vero E6 cells	[22]
Hesperetin	Inhibition of SARS-CoV 3CLpro	8.3 μM and 60 μM in cell-based and cell-free assays respectively	2718 μM	327.5 and 45.3 in cell-based and cell-free assays respectively	Cell-free assay using recombinant 3CLpro fusion protein and substrate Cell-based assay using recombinant 3CLpro–substrate–luciferase fusion protein	[25]
Amentoflavone	Inhibition of SARS-CoV 3CLpro	8.3 μM	-	-	FRET assay using commercial 3CLpro	[26]
GCG and EGCG	Inhibition of SARS-CoV 3CLpro	GCG: 47 μM EGCG: 73 μM	-	-	FRET assay using recombinant 3CLpro	[27]
Herbacetin, Rhoifolin and Pectolinarin	Inhibiton of SARS-CoV 3CLpro	Herbacetin: 33.17 μM Rhoifolin: 27.45 μM Pectolinarin: 37.78 μM	-	-	FRET assay using recombinant SARS-CoV 3CLpro	[28]
Psoralidin and Isobavachalcone	Inhibition of SARS-CoV PLpro	Psoralidin: 4.2 ± 1.0 μM Isobavachalcone: 7.3 ± 0.8 μM	-	-	Fluorescence-based assay using a fluorogenic substrate and recombinant SARS-CoV PLpro	[29]
Herbacetin, Isobavachalcone, and Helichrysetin	Inhibition of MERS-CoV 3CLpro	Herbacetin: 40.59 μM Isobavachalcone: 35.85 μM Helichrysetin: 67.04 μM	-	-	FRET assay using recombinant MERS-CoV 3CLpro	[30]
Quercetin	Inhibition of helicase activity of SARS-CoV NSP13	Quercetin: 8.1 μM	-	-	FRET-based assay for the DNA unwinding activity of helicase	[32]
Myricetin and Scutellarein	Inhibition of ATPase activity of SARS-CoV NSP13	Myricetin: 2.71 ± 0.19 μM Scutellarein: 0.86 ± 0.48 μM	-	-	Colorimetric-based ATP hydrolysis assay	[33]
Quercetin	Inhibition of SARS-CoV-2 3CLpro	-	-	-	FRET assay using recombinant SARS-CoV-2 3CLpro	[34]
EGCG	Inhibition of SARS-CoV-2 3CLpro	0.874 ± 0.005 μM	-	-	FRET assay using recombinant SARS-CoV-2 3CLpro	[35]
EGCG	Inhibition of viral entry by blocking the binding of SARS-CoV-2 S protein to ACE2	3.77  μM	-	-	Plaque reduction assay using live SARS-CoV-2	[36]
EGCG	Inhibition of endoribonuclease activity of SARS-CoV-2 Nsp15	1.62 µM and 0.2 µM in enzymatic assay and live virus infection assay respectively	-	-	FRET assay using recombinant NSP15 and live SARS-CoV-2 palque reduction assay	[37]
GCG	Inhibition of binding of SARS-CoV-2 N protein to viral RNA	44.4 µM	155.4 µM	3.5	SARS-CoV-2 infection of A549-hACE2 cells	[38]
Herbacetin, Pectolinarin	Inhibition of SARS-CoV-2 3CLpro	Herbacetin: 53.90 µM Pectolinarin: 51.64 µM	-	-	FRET assay using recombinant SARS-CoV-2 3CLpro	[39]
Myricetin	Inhibition of SARS-CoV-2 3CLpro	3.684 ± 0.076 μM	-	-	FRET assay using recombinant SARS-CoV-2 3CLpro	[40]
Quercetin	Inhibition of ACE2	4.48 µM	-	-	FRET assay using recombinant ACE2 and Mca-APK(Dnp) as the substrate	[41]
Resveratrol	Inhibition of MERS-CoV viral RNA replication, nucelocapsid protein expression, and MERS-CoV-mediated cell apoptosis Inhibiton of SARS-CoV-2 viral entry	4.48 µM	>200 µM	>45	Live MERS-CoV infection assays such as plaque assay, MTT, and neutral red uptake assay as well as immunofluorescent assay Live SARS-CoV-2 infection of Vero cells	[43] [44]