Review Article

Natural Antioxidants: A Review of Studies on Human and Animal Coronavirus

Table 2

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

AntioxidantType of cells testedConcentration (IC50)Antiviral effectMechanism of actionReference

(+)-CatechinTGEV-infected ST cells(+)-Catechin (20–80 μM)Inhibition of TGEV-induced apoptosisSuppression of the TGEV-induced Bcl-2 reduction, Bax redistribution, cytochrome c release, and caspase-3 activation[107]
ResveratrolMERS-infected Vero E6 cells.Resveratrol (125-250 μM)Inhibition of MERS-induced infection/apoptosis and prolonged cellular survival after virus infectionReduction 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 GS115Quercetin (73 μM)
Epigallocatechin gallate (73 μM)
Gallocatechin gallate (47 μM)
Inhibition of coronavirus replicationGCG 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 cellsQ7R (10 μM)Reduction of the formation of a visible cytopathic effect (CPE) without DNA fragmentationNot 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 replicationFlavonoids exhibited SARS-CoV 3CLpro inhibitory activity[113, 112, 111]
Herbacetin, isobavachalcone, quercetin 3-β-d-glucoside, helichrysetinTryptophan-based fluorescence methodHerbacetin (40.59 μM)
Isobavachalcone (35.85 μM)
Quercetin 3-β-d-glucoside (37.03 μM)
Helichrysetin (67.04 μM)
Inhibition of MERS-CoV replicationFlavonoids exhibited MERS-CoV 3CLpro inhibitory activity[117]
Isobavachalcone
Psoralidin
Lineweaver–Burk and Dixon plotsIsobavachalcone (7.30 μM)
Psoralidin (4.02 μM)
Inhibition of SARS-CoV replicationIsobavachalcone and psoralidin exhibited SARS-CoV papain-like protease inhibitory activity[115]
Myricetin, scutellareinSPR/FRET-based bioassaysMyricetin (2.71 μM)
Scutellarein (0.86 μM)
Inhibition of SARS-CoV replicationMyricetin and scutellarein potently inhibit the SARS-CoV helicase protein in vitro by affecting the ATPase activity[116]