Table 1.

Target Mechanisms of Drug Discovery From Natural Resources for COVID-19 With Example Studies.

	Source	Phytochemical	Structure of Phytochemicals	Study design	Mechanism	Ref
Hand hygiene	Aloe vera (L.) Burm.f.	Aloin and aloe- emodin		In vitro	Inhibiting the viral replication or destructing the virus lipid envelope	26
	Melaleuca alternifolia (Maiden & Betche) Cheel.	Terpenes		In vitro	Disrupting the viral membrane fusion procedure and viral replication	25
Pre-exposure immunomodulation	Allium sativum L. (garlic)			Animal (Rat)	Boosting immune system cells and suppressing production of proinflammatory cytokines	20, 22
Virus binding and entry	Ammoides verticillata (Desf.) Briq.	Isothymol		In silico	ACE inhibitors	30
	Nigella sativa L.	Dithymoquinone (DTQ)		In silico	ACE2 inhibitor	33
	Glycyrrhiza glabra L.	Glycyrrhizin		In silico	ACE2 inhibitor	85
	Propolis	Myricetin, Caffeic acid phenethyl ester, Hesperetin, Pinocembrin		In silico	Inhibitory potential with high binding energy to ACE2 (-8.97 kcal/mol)	86
		Kaempferol		In silico	Inhibitory potential with high binding energy to ACE2 (-7.5 kcal/mol)	87
		Quercetin		In silico	Inhibitory potential with high binding energy to ACE2 (-10.4 kcal/mol)	88
	Withania somnifera (L.) Dunal (Ashwagandha)	Withaferin-A, Withanone, Caffeic acid phenethyl ester		In silico, In vitro (MCF7 cells)	TPMRSS2 inhibition	28
	Ziziphus rugosa Lam.	Rugosanine B		Computational screening	Cathepsin L inhibition	2
	Senna occidentalis (L.) Link	Ararobinol		Computational screening	Cathepsin L inhibition	2
	Hypecoum pendulum L.	(+)- oxoturkiyenine		Computational screening	Cathepsin L inhibition	2
	Cinchona calisaya Wedd.	3α,17α-cinchophylline		Computational screening	Cathepsin L inhibition	2
	Clerodendrum trichotomum Thunb.	Trichotomine		Computational screening	Cathepsin L inhibition	2
	Tectona grandis L.f.	Tectol		Computational screening	Cathepsin L inhibition	2
	Silybum marianum (L.) Gaertn.	Silymonin		Computational screening	Cathepsin L inhibition	2
	Picrasma quassioides (D.Don) Benn.	Picrasidine M		Computational screening	Cathepsin L inhibition	2
	Juglans regia L.	Juglone		Computational screening	Cathepsin L inhibition	2
Viral replication	Tinospora cordifolia (Willd.) Miers	Berberine		In silico	Inhibition of 3CLpro function	45
	Anthemis hyalina DC.			In vitro (HeLa- CEACAM1a cells)	Inhibition of TRP gene expression	57
	Asparagus racemosus Willd.			In silico	Inhibition of N protein	48
	Glycyrrhiza glabra L.	Glycyrrhizin		In vitro	Inhibition of viral replication	56
Immunomodulation and anti­inflammation	Lophatherum gracile Brongn.			In vivo	Enhancement of CD4+/CD8+ T cell ratio, inhibition of IL-Ιβ, TNF- α, and IFN-γ expression	74
	Panax ginseng C.A.Mey.	Ginsenoside Rg1			Enhancement of CD4+ T cell activity	72
	Tanacetum parthenium (L.)	Parthenolide		In vitro, In vivo	Inhibition of IL-1, IL-2, IL-6, IL-8, and TNF-α expression	79
	Sch.Bip. (feverfew)
	Viscum album L.			In vitro	Enhancement of CD4+ T cell migration	75
	Scutellaria baicalensis Georgi			In vivo	Inhibition of IL-1beta, IL- 2, IL-6, IL-12 and TNF-α expression	76
	Propolis	Caffeic acid, and Caffeic acid phenethyl ester			Downregulation and inhibition of PAK1	35
	Biophytum umbraculum Welw.			In vitro (RAW 264.7 cell line)	Anticomplement and anti­inflammatory effects	89
Anticomplement	Citrus aurantium L. var. amara Engl.	Eriocitrin/ neoeriocitrin, rhoifolin, hesperidin, naringin, rutin, veronicastroside, neohesperidin, and hesperetin		In vitro	Anticomplement and anti­inflammatory effects	81