Table 2.

Natural antioxidants tested in in vitro coronavirus infection models and their main results and mechanism of action.

Antioxidant	Type of cells tested	Concentration (IC50)	Antiviral effect	Mechanism of action	Reference
(+)-Catechin	TGEV-infected ST cells	(+)-Catechin (20–80 μM)	Inhibition of TGEV-induced apoptosis	Suppression of the TGEV-induced Bcl-2 reduction, Bax redistribution, cytochrome c release, and caspase-3 activation	[107]
Resveratrol	MERS-infected Vero E6 cells.	Resveratrol (125-250 μM)	Inhibition of MERS-induced infection/apoptosis and prolonged cellular survival after virus infection	Reduction of the expression of nucleocapsid (N) protein essential for MERS-CoV replication	[118]
Quercetin Epigallocatechin gallate Gallocatechin gallate (GCG)	Recombinant 3CLpro was expressed in Pichia pastoris GS115	Quercetin (73 μM) Epigallocatechin gallate (73 μM) Gallocatechin gallate (47 μM)	Inhibition of coronavirus replication	GCG displayed a binding energy of -14 kcal mol−1 to the active site of 3CLpro and the galloyl moiety at 3-OH position was required for 3CLpro inhibition activity	[114]
Quercetin 7-rhamnoside (Q7R)	PEDV-infected Vero cells	Q7R (10 μM)	Reduction of the formation of a visible cytopathic effect (CPE) without DNA fragmentation	Not specificity	[105, 106]
Amentoflavone Apigenin Luteolin Quercetin Quercetin 3-β-galactoside Herbacetin Rhoifolin Pectolinarin	SARS-CoV 3CLpro inhibition using fluorescence resonance energy transfer analysis Molecular docking, SPR/FRET-based bioassays, and mutagenesis Tryptophan-based fluorescence method	Amentoflavone (8.3 μM) Apigenin (208.8 μM) Luteolin (20.2 μM) Quercetin (23.8 μM) Quercetin 3-β-galactoside (5-200 μM) Herbacetin (33.17 μM) Rhoifolin (27.45 μM) Pectolinarin (37.78 μM)	Inhibition of SARS-CoV replication	Flavonoids exhibited SARS-CoV 3CLpro inhibitory activity	[113, 112, 111]
Herbacetin, isobavachalcone, quercetin 3-β-d-glucoside, helichrysetin	Tryptophan-based fluorescence method	Herbacetin (40.59 μM) Isobavachalcone (35.85 μM) Quercetin 3-β-d-glucoside (37.03 μM) Helichrysetin (67.04 μM)	Inhibition of MERS-CoV replication	Flavonoids exhibited MERS-CoV 3CLpro inhibitory activity	[117]
Isobavachalcone Psoralidin	Lineweaver–Burk and Dixon plots	Isobavachalcone (7.30 μM) Psoralidin (4.02 μM)	Inhibition of SARS-CoV replication	Isobavachalcone and psoralidin exhibited SARS-CoV papain-like protease inhibitory activity	[115]
Myricetin, scutellarein	SPR/FRET-based bioassays	Myricetin (2.71 μM) Scutellarein (0.86 μM)	Inhibition of SARS-CoV replication	Myricetin and scutellarein potently inhibit the SARS-CoV helicase protein in vitro by affecting the ATPase activity	[116]