Table 2.

Effect of phytocompounds on targeted SARS-CoV-2 proteins/replication/infection in cell-free and cell-based studies.

Sl no	Crude extract/compound	Virus/RNA/enzyme inhibition/cytotoxicity	Inhibitory assay	Dosage (IC50/EC50/CC50)		References
Flavonoid
01	Baicalein	3CLpro -	Invitro	IC50	0.39 ± 0.11 μM	[50]
		SARS-CoV-2 replication	Vero cells	EC50	2.92 ± 0.06 μM	[50]
		Cytotoxicity	Vero cells	CC50	>500 μM	[50]
02	Baicalin	3CLpro	In-vitro	IC50	83.4 ± 0.9 μM	[50]
03	Scutellarein	3CLpro	In-vitro	IC50	5.80 ± 0.22 μM	[50]
04	Dihydromyricetin	3CLpro	In-vitro	IC50	1.20 ± 0.09 μM	[50]
05	Quercetagetin	3CLpro	In-vitro	IC50	1.24 ± 0.14 μM	[50]
06	Myricetin	3CLpro	In-vitro	IC50	2.86 ± 0.23 μM	[50]
07	Baicalin	3CLpro (FRET)	In-vitro	IC50	6.41 ± 0.95 μM	[78]
		Replication inhibition	Vero E6	EC50	27.87 ± 12.95 μM	[78]
		Cytotoxicity	Vero E6	CC50	>200 μM	[78]
08	Baicalein	3CLpro (FRET)	In-vitro	IC50	0.94 ± 0.20 μM	[78]
		Replication	Vero E6	EC50	2.94 ± 1.19 μM	[78]
		Cytotoxicity	Vero E6	CC50	>200 μM	[78]
09	Theaflavin	3CLpro (FRET)	In-vitro	IC50	8.44 μg/mL	[39]
		Cytotoxicity	HEK293T	CC50	>40 μg/mL	[39]
10	Myricetin	3CLpro (FRET)	In-vitro	IC50	0.2 μM	[107]
11	Baicalin	3CLpro (FRET)	In-vitro	IC50	34.71 μM	[103]
12	Herbacetin	3CLpro (FRET)	In-vitro	IC50	53.90 μM	[103]
13	Pectolinarin	3CLpro (FRET)	In-vitro	IC50	51.64 μM	[103]
Terpenoids
14	Glycycrrhizin (triterpenoid saponin)	3CLpro	In-vitro	IC50	30 μM (0.024 mg/mL)	[86]
		Virus titer tit	Vero cells	TCID50	0.44 mg/mL	[86]
		Cytotoxicity	Vero cells		4 mg/mL (no cytotoxicity)	[86]
15	Δ9-Tetrahydro cannabinol	Antiviral activity	Vero cells	EC50	13.17 μM	[97]
		Cytotoxicity	Vero cells	CC50	29.34 μM	[97]
16	Δ9 -THC	Antiviral activity	Vero cells	EC50	10.25 μM	[97]
		Cytotoxicity	Vero cells	CC50	25.79 μM	[97]
17	CBN	Antiviral activity	Vero cells	EC50	11.07 μM	[97]
		Cytotoxicity	Vero cells	CC50	19.9 μM	[97]
18	CBD	Antiviral activity	Vero cells	EC50	7.91 μM	[97]
		Cytotoxicity	Vero cells	CC50	16.72 μM	[97]
19	CBDA	Antiviral activity	Vero cells	EC50	37.61 μM	[97]
		Cytotoxicity	Vero cells	CC50	59.53 μM	[97]
20	Andrographolide	SARS-CoV2 infection in-vitro	Vero E6	EC50	6.58 μM	[42]
		Plaque reduction	Vero E6	EC50	0.28 μM
		Cytotoxicity		CC50	27.77 μM
21	Andrographolide	Plaque reduction	Calu-3 cells	EC50	0.034 (μM)	[72]
		Cytotoxicity	a) HepG2 b) imHC c) HK-2 d) Caco-2 e) Calu-3 f) SH-SY5Y	CC50 CC5 CC5 CC5 CC5 CC5	a) 81.52 μM b) 44.55 μM c) 34.11 μM d) 52.30 μM e) 58.03 μM f) 13.19 μM
22	Arteether (sesquiterpene lactone)	SARS-CoV-2 infection	Vero E6	EC50	31.86 ± 4.72 μM	[14]
		Cytotoxicity	Vero E6	CC50	>200 μM	[14]
23	Artemether (sesquiterpene lactone)	SARS-CoV-2 infection	Vero E6	EC50	73.80 ± 26.91 μM	[14]
		Cytotoxicity	Vero E6	CC50	>200 μM	[14]
24	Artemisic acid (sesquiterpene lactone)	SARS-CoV-2 infection	Vero E6	EC50	>100 μM	[14]
		Cytotoxicity	Vero E6	CC50	>200 μM	[14]
25	Artemisinin (sesquiterpene lactone)	SARS-CoV-2 infection	Vero E6	EC50	64.45 ± 2.58 μM	[14]
		Cytotoxicity	Vero E6	CC50	>200 μM	[14]
26	Artemisone (sesquiterpene lactone)	SARS-CoV-2 infection	Vero E6	EC50	49.64 ± 1.85 μM	[14]
		Cytotoxicity	Vero E6	CC50	>200 μM	[14]
27	Dihydroartemisinin (sesquiterpene lactone)	SARS-CoV-2 infection	Vero E6	EC50	13.31 ± 1.24 μM	[14]
		Cytotoxicity	Vero E6	CC50	31.44 ± 0.73 μM	[14]
28	Artesunate (sesquiterpene lactone)	SARS-CoV-2 infection	Vero E6	EC50	12.98 ± 5.30 μM	[14]
		Cytotoxicity	Vero E6	CC50	55.08 ± 2.32 μM	[14]
29	Arteannuin (sesquiterpene lactone)	SARS-CoV-2 infection	Vero E6	EC50	10.28 ± 1.12 μM	[14]
		Cytotoxicity	Vero E6	CC50	71.13 ± 2.50 μM	[14]
30	Cannabidinol	SARS-CoV-2 infection	Vero E6	CC50	71.13 ± 2.50 μM 1.25 μM (SARS CoV2γ) 0.85 μM (SARS CoV2α) 0.86 μM (SARS CoV2β) 0.63 μM (SARS CoV2)	[14] [61]
		Cytotoxicity	A549-ACE2	EC50
Tannins
31	Punicalin	RBD-ACE2 binding assay (ELISA)	Invitro	IC50	0.14 mg/mL	[80]
32 33 34 35 36 37 38	Corilagin Corilagin Corilagin (RAI-S-37) Corilagin (RAI-S-37) + Remidesivir Corilagin (RAI-S-37) Corilagin (RAI-S-37) Corilagin (RAI-S-37)	SARS-CoV-2 inhibition RBD-ACE2 binding assay (ELISA) Cytotoxicity Cytotoxicity Cytotoxicity SARS-CoV-2 RdRp inhibition SARS-CoV-2 RdRp inhibition SARS-CoV-2 RdRp inhibition SARS-CoV-2 RdRp inhibition SARS-CoV-2 infection	Vero In-vitro HEK293 cell LO2 cells Beas-2B cell HEK293 cell transfected with nsp7 + nsp8 + nsp12 HEK293 transfected with nsp7 + nsp8 + nsp12 HEK293 transfected with nsp7 + nsp8+nsp12/nsp10+nsp14 HEK293 transfected with nsp7 + nsp8+nsp12/nsp10+nsp14 Vero cells	EC50 IC50 CC50 CC50 CC50 EC50 EC50 EC50 EC50 EC50	0.13 μmol/L 24.9 μM >100 >100 >100 3.33 ± 0.52 μmol/L 1.25 ± 0.52 μmol/L 3.65 ± 0.56 μmol/L 1.84 ± 0.27 μmol/L 0.13 μmol/L	[108] [93] [93] [108] [108] [108] [108]
39	EGCG	3CLpro (FRET)	In-vitro	IC50	7.58 μg/mL	[39]
		Cytotoxicity	HEK293T	CC50	>40 μg/mL
Others
40	Cepharanthine (alkaloid)	SARS-CoV2 infection	Vero cells	EC50	2.8 μM	[38]
				CC50	12.9 μM
41	Emetine (alkaloid)	SARS-CoV2 infection	Vero cells	EC50	0.000397 μM	[38]
				CC50	1.53 e + 6 μM
42	6-Gingerol (beta-hydroxy ketone)	SARS-CoV2 infection	Vero E6	EC50	>100 μM	[42]
		Cytotxicity	Vero E6	CC50	>100 μM
43	Panduratin A (Diarylheptanoid)	SARS-CoV2 post infection	Vero E6	EC50	0.81 μM	[42]
			Vero E6	CC50	14.71 μM
		SARS-CoV2 pre-entry	Vero E6	EC50	5.30 μM
			Vero E6	CC50	43.47 μM
		Plaque reduction	Vero E6	EC50	0.078 μM
		SARS-CoV2 infection	Calu3	EC50	2.04 μM
		Cytotoxicity	Calu3	CC50	43.92 μM
		Plaque reduction	Calu3	EC50	0.53 μM
44	Emetine hydrochloride (alkaloid)	SARS-CoV-2 virus reduction	Vero E6	EC50	0.46 μM	[111]
		CPE inhibition	Vero E6	EC50	1.5625 μM	[111]
		Cytotoxicity	Vero E6	CC50	56.46 μM	[111]
45	Phillyrin (KD-1) Lignan)	Anti-HCoV-229E	Vero E6	EC50	64.53 μg/ml	[113]
		Cytopathic effect	Vero E6	EC50	63.90 μg/ml	[113]
		Cytotoxicity	Vero E6	CC50	1959 μg/ml	[113]
			Huh7	CC50	1034 μg/ml	[113]
		Reduce the production of proinflammatory cytokines	Vero E6	–CPE (cytopathic effect)	(250, 125, and 62.5 μg/ml of KD1) TNF-α, IL-6, IL-1β, MCP-1, and IP-10) at the mRNA levels.	[113]
46 47	Cepharanthine (bisbenzylisoquinoline alkaloid) Lycorine (alkaloid)	SARS-CoV-2 RNA	VeroE6/TMPRSS2	EC50	0.35 μM,	[114]
		Cytotoxicity SARS-CoV-2 infection	VeroE6/TMPRSS2 Vero cells	CC50 EC50	25.1 μM 0.878 μM	[114] [112]
48	Digoxin (cardiotonic glycoside)	SARS-CoV-2 infection	Vero cells	EC50	0.043 μM	[110]
		Cytotoxicity	Vero cells	CC50	>10 μM	[110]
49 50 51 52	Ouabain (Cardiac glycoside similar to digitoxin) Herbacetin Pectolinarin Rhoifolin	SARS-CoV-2 infection	Vero cells	EC50	0.024 μM	[110]
		Cytotoxicity 3CLpro (FRET) 3Clpro (FRET) 3CLLpro (FRET)	Vero cells in-vitro in-vitro in-vitro	CC50 IC50 IC50 IC50	>10 μM 33.17 μM 27.45 μM 37.78 μM	[110] [71]
Crude extracts
53	Andrographis paniculata extract	SARS-CoV2 infection	Vero E6	EC50	68.06 μg/ml	[42]
		Cytotoxicity		CC50	>100 μg/ml
54	Andrographis paniculata extract	Plaque assay	Calu-3 cells	EC50	0.036 (μg/mL)	[72]
55	Zingiber officinale rhizome extract	Inhibition of SARS-CoV2 infection	Vero E6	EC50	29.19 μg/ml	[42]
		Cytotoxicity	Vero cells	CC50	52.75 μg/ml
		Plaque reduction	Vero cells	EC50	1.45 μg/ml
56	Boesenbergia rotunda (extract)	SARS-CoV2 infection	Vero cells	EC50	3.62 μg/mL	[42]
			Vero cells	CC50	28.06 μg/mL
57 58	Scutellaria baicalensis extract Pomegranate peel extract	3CLpro assay	In-vitro	IC50	8.52 ± 0.54 μg/mL	[50]
		SARS CoV2 RNA replication	Vero cells	EC50	0.74 ± 0.36 μg/mL	[50]
		Cytotoxicity RBD-ACE2 binding assay (ELISA)	Vero cells In-vitro	CC50 IC50	>500 μg/mL 0.06 mg/mL	[80]